Neuroscience and Biobehavioral Reviews 35 (2011) 18541863

Contents lists available at ScienceDirect

Neuroscience and Biobehavioral Reviews
j our nal homepage: www. el sevi er . com/ l ocat e/ neubi or ev
Review
Octodon degus. A useful animal model for social-affective neuroscience research:
Basic description of separation distress, social attachments and play
Valentina Colonnello
a,b,
, Paolo Iacobucci
a,b
, Thomas Fuchs
c
, Ruth C. Newberry
a
, Jaak Panksepp
a
a
Center for the Study of Animal Well-being, Department of Veterinary & Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman,
WA 99164-6520, United States
b
Department of Psychology, University of Rome Sapienza, Rome 00185, Italy
c
Biology Department, Pennsylvania State University, State College, PA 16802, United States
a r t i c l e i n f o
Article history:
Received 17 November 2010
Received in revised form 16 March 2011
Accepted 25 March 2011
Keywords:
Model
Attachment
ADHD
Depression
Anxiety
Emotional development
Externalizing and internalizing disorders
a b s t r a c t
A challenge for social-affective neuroscience programs is to identify simple and yet valid animal mod-
els for studying the expression of basic social emotions and their role during different developmental
windows, from infancy to adulthood. For example, although laboratory rats are useful for studying
juvenile social interactions, they are not ideal for studying infant attachment bonds. Here, we eval-
uate current understanding of the social behavior of Octodon degus, a diurnal precocial rodent, to
elucidate the value of this species as a model for social-affective neuroscience research. After a syn-
opsis of species-specic characteristics and brain susceptibility to changes of social environment, our
behavioral ndings on degu social proclivities are summarized. We then discuss why this pre-clinical
model provides a valuable addition to the commonly available animal models for the study of human
psychopathology.
2011 Elsevier Ltd. All rights reserved.
Contents
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1854
2. Species characteristics, social phenotypes, and ecology of degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1855
3. Brain sensitivity to changes of social environment in degus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1856
4. Social bonds and effects of social isolation in infant degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1856
4.1. Responses to acute social isolation stress in early infancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1857
4.2. Responses to chronic social isolation stress in early infancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1858
5. Peer interactions and their role on socio-emotional development in juvenile degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1859
5.1. Peer interactions in juvenile degus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1859
5.2. Effects of deprivation of peer interactions during the play period . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1859
5.3. Effects of deprivation of peer interactions since early adolescence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1860
6. Methodological considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1860
7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1861
Acknowledgements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1861
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1861

Corresponding author at: Department of Veterinary & Comparative Anatomy,

Pharmacology and Physiology, Washington State University, Pullman, WA 99164-
6520, United States.
E-mail addresses: vcolonnello@vetmed.wsu.edu, valentina.colonnello@gmail.
com (V. Colonnello), iacobucci@vetmed.wsu.edu (P. Iacobucci), tfuchs@pitt.edu
(T. Fuchs), rnewberry@wsu.edu (R.C. Newberry), jpanksepp@vetmed.wsu.edu
(J. Panksepp).
1. Introduction
The distress response of an isolated infant, the rough-and-
tumble play between juveniles, and the prompt care behavior
directed towards a newborn are clear expressions of basic emo-
tions rooted in subcortical neural circuits found across mammalian
species (see MacLean, 1985, 1990; Panksepp, 1998, 1982, 2005,
0149-7634/$ see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.neubiorev.2011.03.014
V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863 1855
for extensive reviews). However, in the few mammalian species
commonly used as pre-clinical neuroscience models, such neuro-
biological urges and competencies are present in varying degrees
(Panksepp et al., 1992; Panksepp, 2003). This variation raises
questions about which species represent appropriate models for
generating principles of brain social organization that translate to
humans.
Altricial rodents have served as valuable models for the study
of important social-affective processes, such as juvenile social
play and adult pair bonding (Aragona and Wang, 2004; Carter
and Getz, 1993; Panksepp et al., 1984; Panksepp, 1998; Pellis
and Pellis, 2007; Vanderschuren et al., 1997; and see Siviy and
Panksepp, in this issue). Laboratory rats and mice, especially,
are commonly used in behavioral research, and the need to
maximize laboratory resources has led to a progressive and exten-
sive use of these altricial rodents with compressed life span for
studying infant lial bonds. Unfortunately, these species show
some limitations when used for this purpose, including relatively
weak responses to social isolation, no clear preference for their
caregiver, and debatable social-separation calls (Panksepp et al.,
1992; Panksepp, 2003, 2005). As a consequence, reliance on these
species may lead to inadvertent biases and limited generaliz-
ability to humans. This was one reason for choosing dogs for
early attempts to decode the neural nature of social bonds (e.g.,
Panksepp et al., 1978). For instance, puppies show motor agita-
tion and emit distress vocalizations (DVs) at high and sustained
rates when abruptly and involuntarily separated from their care-
givers (Panksepp et al., 1978; Topl et al., 1998). In dogs, and
social primates such as rhesus monkeys (Bayart et al., 1990), infant
responses to social isolation are robust, selective, and persistent,
but extensive use of these species as laboratory subjects is imprac-
tical.
In this article, we summarize our work with a new behavioral
model, the degu (Octodon degus), a diurnal and precocious rodent.
This species has a relatively compressed developmental life span,
together with a highly evolved social organization that in some
ways may resemble ancestral humans (e.g., group mothering by
aunts, Hrdy, 2009). Our hope was that the degu may represent a
relevant and economically feasible model for the study of infant
attachment bonds as well as juvenile peer interactions. We were
especially motivated to invest in characterizing the social behavior
of degus by the remarkable discoveries by Katharina Brauns group
at the University of Magdeburg (vide infra) demonstrating brain
sensitivities in this species to various interesting social challenges
and variables.
After an overview of the social characteristics of O. degus as
well as experimentally induced brain changes in socially isolated
degus, we present a synopsis of our behavioral work on infant
and juvenile degus, which leads us to consider this species as
an attractive model for the study of social-affective bonds across
developmental stages. We then consider whether the degu is a
feasible animal model for the study of human psychopathology
according to classic validity criteria. If so, known risk factors for the
emergence of human psychopathology should induce correspond-
ing pathological changes in degu behavior (causative validity). In
addition, an optimal small-animal model should display behav-
iors potentially homologous to human clinical symptoms (face
validity), and conform to theoretical models of clinical condi-
tions (construct validity). Moreover, therapeutic treatments for
humanpsychopathologyshouldleadtosimilar results intheanimal
model (predictive validity) (McKinney and Bunney, 1969; Redei
et al., 2001). In short, now that brain control of social bonds
and urges that resemble attachments in our own species has
become of great interest to many investigators, the eld is in need
of more valid, yet efcient, models of socio-emotional develop-
ment.
2. Species characteristics, social phenotypes, and ecology of
degus
O. degus (the trumpet-tailed or brush tailed rat or degu) is a
hystricomorph rodent endemic to the semi-arid regions of north-
central Chile (Fulk, 1976). Although colony size is variable, colonies
typically comprise 46 adult females, 12 adult males, plus young
fromthe current andprevious litters (Fulk, 1976; Hayes et al., 2009;
Wilson, 1982). Relatedness of colony members is also variable,
ranging from0.07 to 0.48 between females in one wild population,
and averaging 0.25 which is equivalent to second-order kinship
(Ebensperger et al., 2004). During the daytime, the group members
roamabove ground and coordinate their foraging activity by keep-
ing visual contact (Ebensperger and Bozinovic, 2000; Ebensperger
et al., 2002; Quirici et al., 2008; Vasquez, 1997) andemittingaudible
vocalizations (Long, 2007). They synchronize their digging activity
to build complex underground burrows, which they share when
night falls, and use routinely as refuges to raise their precocious
but unweaned pups (Ebensperger et al., 2004; Fulk, 1976; Lee,
2004).
Degus are polygynous, plural breeders, exhibiting synchronous
breeding in combination with communal nesting and nursing
(Ebensperger et al., 2002, 2004). Adult resident males aggressively
defend their harem from intruding males in the breeding season
whereas they are more tolerant at other times of year (Soto-
Gamboa et al., 2005). After a gestation period of about 90 days,
colonyfemales typicallygivebirthtolitters of 48pups (range112
pups). Mothers contribute to the rearing of all pups in the commu-
nal nest (Ebensperger et al., 2007), but they provide more milk to
their own young, and those of close relatives, than to the young of
non-relatives (Jesseau et al., 2009). Unlike most laboratory rodents,
and similar to prairie voles (Carter and Getz, 1993), males also par-
ticipate in rearing of the young. Although the extent of paternal
investment remains to be well documented, laboratory observa-
tions have shown that fathers huddle with the pups soon after
birth and subsequently regulate their social interactions (Wilson,
1982). Furthermore, under laboratory conditions, neither males
nor females have been observed to direct agonistic or infanticidal
behavior towards infants, even when unrelated and socially unfa-
miliar (Ebensperger, 2001). Communal pup care does not appear
to translate into an overall improvement in postnatal survival and
growth of pups relative to solitary breeding (Ebensperger et al.,
2007; Hayes et al., 2009), suggestive of interesting social dynamics
affecting individual reproductive tness within colonies.
In contrast to altricial rodents, degus are born with open eyes,
a functional auditory system, and an immediate ability to move
around the nest (Fox, 1965; Jamon, 2006; Reynolds and Wright,
1979). Thus, similar to human infants, newborn degus are able to
perceive acoustic and visual information from their social envi-
ronment and interact in rich ways with their littermates and
colony mates soon after birth (Reynolds and Wright, 1979). This,
of course, is of great benet for studies conducted early in life,
when potentially confounding prior developmental effects are rel-
atively minimal. Despite their maturity at birth, degus have an
extended period of infancy and adolescence, like primates, during
which they showclose dependence on apparently well-recognized
family members. Although infants are able to maintain their body
temperature autonomously and chew solid food by the sixth day
of life (Reynolds and Wright, 1979), and the time spent nursing
is signicantly reduced by the third week (20% on postnatal day
21), weaning does not occur before the fourth to sixth postnatal
week (Pinkernelle et al., 2009; Reynolds and Wright, 1979; Weir,
1970). Degus exhibit philopatry, with offspring often remaining in
the natal colony into adulthood (Quirici et al., 2010), suggesting an
extendedperiodof social dependenceinthis species, unlikedomes-
tic rats andmice. Limitedevidence suggests that dispersal decisions
1856 V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863
by both males and females are inuenced by social competition
(Quirici et al., 2010).
The interactions of degus are characterized by a rich vocal
repertoire in the audible range, which contrasts with the lim-
ited variety of vocalizations found in common laboratory rodent
species. For example, mice emit no alarm calls during forag-
ing activity (Blanchard et al., 2001) and domestic rat and mouse
mothers emit no vocalizations specic to nursing bouts. Further-
more, although social proximity with females (not just mothers)
inhibits DVs, infant rats and mice emit no calls specic to reunion
with caregivers. By contrast, degus use a variety of vocalizations
to adjust their level of social proximity during all developmental
stages. For instance, isolated degu pups emit whistle DVs which,
in early development, induce retrieval by adults (Fuchs et al., 2010;
Long, 2007). Once reunited with their mother, degu infants emit
specic reunion calls, which are characterized by 4-kHz chirp-
ing components (Iacobucci, personal observation). Lactating degu
females emit characteristic nursing calls, termed mothering calls,
that elicit suckling behavior and regulate nursing bouts (Braun and
Scheich, 1996). Mothering calls and reunion calls are reported
only in mammals with a strongly developed social organization,
such as monkeys (Kalin et al., 1995; Roush and Snowdon, 2001)
and domestic pigs (Colonnello et al., 2010; Illmann et al., 2002).
Degu pups exhibit clear bouts of rough-and-tumble play, which is
also well developed in most domestic rats, but not domestic mice.
When degu pups playfully interact with their siblings, they emit a
variety of vocalizations, including warble calls (Long, 2007) that
resemble their reunion calls, and when interactions between sib-
lings become too vigorous, perhaps verging into aggression, the
father squeaks at the pups and appears to actively separate them
(Wilson, 1982). During foraging, degus emit specic alarm calls
(Long, 2007), and the social interactions of adults and adolescents
are accompanied by a diversity of warbling, whistling and grunting
noises (characterized by Long, 2007).
The aforementioned factors, namely maturity at birth, slow
development, and complex social organization, allow degu pups
to engage in a variety of social interactions over a prolonged period
of development and to establish comparatively sophisticated and
exible social competencies. These same factors, in combination
with a generally docile temper, relatively small size as well as ease
of breeding and maintenance, make this species a potentially ideal
laboratory model for social-affective behavioral and neuroscience
research into the nature of separation distress, social bonds, juve-
nile play and other aspects of prosociality.
3. Brain sensitivity to changes of social environment in
degus
Over the last two decades, signicant progress has been made
in characterizing brain changes that occur in infant and adoles-
cent degus in response to social isolation stress. A series of studies
conducted by Katharina Braun and colleagues demonstrated that
social deprivation during the rst weeks of life induces a host of
neurophysiological and neuroanatomical changes at cortical and
subcortical levels in the brains of young degus. The deprivation
procedure consistedof repeatedepisodes of isolationfromthe fam-
ily unit during the rst three postnatal weeks followed by early
weaning and individual housing at postnatal day (PND) 21. At PND
45, deprived animals showed altered balance between serotonin-
ergic and dopaminergic innervation in several subregions of the
medial prefrontal cortex. In particular, deprived animals showed
higher synaptic density in the infralimbic cortex (Ovtscharoff and
Braun, 2001), altered number and density of tyrosine hydroxylase
immunoreactive neurons (Braun et al., 2000; Poeggel et al., 2003),
and a reduced number of NADPH-diaphorase-containing neurons
in the limbic system (Poeggel et al., 1999) compared to socially
housed, unhandled degus. Other studies controlling for handling
manipulations conrmed these earlier ndings and also showed
that early social isolation is associated with altered serotoninergic
transmission (Jezierski et al., 2006) and altered spine densities in
several regions of the limbic system (Helmeke et al., 2001). Similar
alterations of emotional brain circuits have been found in humans
growing up in adverse environments.
Interestingly, humans show a certain degree of resilience and
brain plasticity when facing adverse life events (Cicchetti et al.,
2007; Glaser, 2000; Kaufman et al., 2004).
Some degree of resilience has also been demonstrated in degus.
Two-week-old degus exposed to brief daily social isolation from
PND 8 to 10 showed an upregulation of glutamate (NMDA),
dopamine (D1), and serotonin (5HT1A) receptor density in several
regions of the limbic system. However, exposure to the playback
of mothering calls emitted by an unfamiliar female counteracted
these brain changes, especially in males (Ziabreva et al., 2000,
2003). This sex difference may mean that females are more depen-
dent on full social contact for affective homeostasis.
Moreover, repeatedsocial separations fromPND1 to 21 induced
a decreased density of calbindin immunoreactive interneurons in
the anterior cingulate and precentral medial subregions of the
medial prefrontal cortex in PND45 degus. However, exposure to an
ensuingperiodof full socializationwithout handlingstress partially
mitigated the effects of the previous stressful experience (Helmeke
et al., 2008).
In sum, many isolation-induced alterations are evident in com-
ponents of the limbic and monoamine neurotransmitter systems,
which are known to be involved in human emotionality. Further-
more, some of these brain alterations resemble those associated
with mood and anxiety disorders. While the vulnerability of the
degu brain to changes in the early social environment is receiv-
ing signicant attention, evidence that early isolation translates
into changes in social behavior, in the short or long term, is scarce.
Therefore, we have devoted effort to the behavioral characteriza-
tion and validation of this animal model.
4. Social bonds and effects of social isolation in infant degus
Our rst aim was to understand whether the degu represents
a useful model for the study of human infant attachment bonds.
According to classical attachment theory, during episodes of invol-
untary social isolation, human infants show a typical protest
response, accompanied by emotional distress and seeking of com-
forting reunions with a caregiver. Initially, infant behaviors are
directed towards anyone in the surrounding area but, once the
attachment bond is established, attachment behaviors become
specically directed towards the caregiver. Infant vocal and motor
efforts are aimed at alleviating distress and reinstating a positive
affective state through restitution of the social reward experienced
during physical closeness to the caregiver. In these efforts, infants
adjust their attachment behaviors in exible ways according to
environmental conditions, caregiver availability, and in anticipa-
tion of a forthcoming reunion (Bowlby, 1969; Cassidy, 1999). These
attachment behaviors lay the foundation for the emergence of a l-
ial attachment bond, which is distinguishable from other forms of
affectional bonds by its persistence and selectivity for the caregiver
(Cassidy, 1999).
When the attachment bond is well established, its disruption
has long-lasting detrimental consequences for an infants socio-
emotional development. After prolonged separation, the infant
protest response ceases and gives way to a continuing depression-
like despair response (Bowlby, 1969; Harlow and Zimmermann,
1959; Kaufman and Rosenblum, 1967; Spitz, 1946), a model for
V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863 1857
depressive disorders that is supported by considerable evidence
(Watt and Panksepp, 2009).
Within this framework, we characterized the exibility and
persistence of protest responses in infant degus to abrupt brief
separations at varying developmental ages. The seeking of prox-
imity to, and selective preference for, the caregiver were also
studied during acute social isolation stress. The consequences of
prolonged, chronic social isolation for infant degu socio-emotional
development were investigated by limiting or eliminating social
interactions after the parentinfant bond was expected to be rmly
established.
4.1. Responses to acute social isolation stress in early infancy
Our rst observations focusedonthedevelopmental timecourse
of infant degu DVs during acute isolation episodes, as an indicator
of the strength of lial attachment. Thirty-eight pups from6 litters
were observed weekly during brief, 15-min periods of social iso-
lation, repeated over the rst seven weeks of life. We detected a
progressive decline of the separation response with age, as indi-
cated by a signicant reduction in the number of DVs emitted
during isolations, from an initial rate of 35489 DVs/15min to
almost zero by the third postnatal week (Fuchs et al., in prepa-
ration). Since these degus were tested repeatedly, habituation to
the test environment likely contributed to the observed decrease.
Indeed, as found in a subsequent experiment controlling for pos-
sible habituation effects (Colonnello et al., in press), young degus
emitted 726 DVs when isolated for 30min for the rst time at
PND 21. Nevertheless, littermates tested for the rst time at PND
31 emitted fewer DVs, indicating that a decline in DVs occurred
with age in the absence of habituation (Colonnello et al., in press).
Young degus also showed exibility in their protest response.
We found that the number of DVs was higher in 3-week-old infant
degus isolated and tested for 30min in a setting consisting of
restricted (fenceline) interactions with the family group through
a wire-mesh grid than in control degus isolated and tested without
social stimuli behindthe grid(32820vs 726.2DVs) (Colonnello
et al., in press). This nding is reminiscent of the observation by
Braun et al. (2003) that 8-day-old degus isolated in an unfamiliar
environment vocalized more when exposed to playback of famil-
iar sounds (i.e., mothering calls emitted by a lactating degu) than
when in complete isolation.
Furthermore, we found that restricted visual and acoustic con-
tact with the family reestablished the isolation response at later
developmental time points (Colonnello et al., in press). In fact, in
a similar setting, some degus emitted DVs as late as PND 56, well
beyond the weaning age (Fuchs, personal observation).
Thus, althoughDVs declinedwithage, theywerepresent for sev-
eral postnatal weeks, indicating persistence of the protest response
to separation throughout developmental ages when the preco-
cial pups are known to leave the nest and might get separated
from the group. In contrast, infant rats and mice stop emitting
DVs around the time when they are motorically mature enough
to get lost on their own (Geyer, 1981). Furthermore, degu infants
solicited family group attention by modulating their DVs according
to the accessibility of social partners, showing exible separation
responses resembling typical human goal-corrected attachment
behaviors (Bowlby, 1969). A similar increase of DVs in response to
unavailable caretakers characterizes most well-bonded species.
For example, human infants emit negative vocalizations during
interactions with an unresponsive mother, such as during a Still-
Face test (Legerstee and Markova, 2007; Tronick et al., 1978), and
rhesus monkeys, squirrel monkeys and domestic pigs emit more
DVs when exposed to an inaccessible mother placed behind a grid
than in full isolation (Bayart et al., 1990; Iacobucci et al., 2008;
Wiener et al., 1990).
Fig. 1. MeanSE % of DVs emitted by infant degus during the two isolation sessions
of a maternal potentiation test. Social contact restores the separation response in a
potentiation paradigm. When degu pups were either placed into an empty chamber
or into one that contained bedding from their home cage between two consecutive
isolations, the number of separation calls declined signicantly from the rst to
the second isolation (non-social conditions, pooled data). In contrast, social contact
witheither the mother or anunfamiliar female resultedinanincrease inthe average
number of separation calls relative to the non social setting during isolation 2 (social
conditions, pooled data) (adapted from Fuchs et al., 2010). *p<0.05.
We also investigated the specicity of the motherinfant bond.
As aforementioned, degus nest and nurse communally, a fact rarely
addressed in studies underscoring similarities between humans
and rodents. It has been demonstrated that adult female degus can
discriminate between their own pups and those of other colony
females based on odor cues (Jesseau et al., 2008). Although lactat-
ing degus will retrieve and nurse unrelated young (Ebensperger
et al., 2006), they apparently use information about pup identity
in the provisioning of milk (Jesseau et al., 2009). To nd out if
infant degus can also recognize their biological mother, we tested
them in a maternal potentiation paradigm. The term potentia-
tion refers to an increase in the number of DVs observed from
one isolation session to the next when pups are allowed brief
contact with their mother between isolations. Although, in labo-
ratory rats, such potentiation was initially assumed to be specic
for the mother it can also be found following exposure to other
social partners (see Shair, 2007 for a full description). We tested
5-day-old degus by exposing them to either non-social (nest odor
or no odor control) or social (mother or unfamiliar non lactating
female) conditions between isolations. During the second isola-
tion, controls and infants previously exposed to nest odor showed
a marked decline in their separation response, while infants previ-
ously exposedtosocial partners emittedDVs at rates comparable to
their rst isolation (Fuchs et al., 2010, Fig. 1). Comparable persis-
tence has beenfoundinother precocious social species (Colonnello
et al., 2010; Hennessy et al., 2006). However, the increased persis-
tence of the separation response in social conditions was observed
at similar levels in both the mother and stranger groups. Similar to
altricial rodent species and unlike guinea pigs, infant degus, there-
fore, did not differentiate between their mother and a stranger in
this test. It remains to be determined whether this lack of behav-
ioral discrimination was observed because attachment bonds were
not fully established in 5-day-old degus or if the maternal potenti-
ation paradigm is not suitable to detect infant-mother recognition
inthis species. This was notedpreviously indomestic pigs, inwhich
reunion responses were better indicators of maternal recognition
(Colonnello et al., 2010).
White et al. (1982) also reported that infant degus could not
discriminate between mothers and lactating strangers in a choice
paradigm, yet they found a seemingly counterintuitive preference
for the stranger that implies discrimination. Observations of pups
of different ages (fromPND10to21) were pooledinthis study, with
a possible confounding effect of age. After further testing we found
1858 V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863
that, when offered a choice between their mother and an unfa-
miliar lactating female, 15-day-old pups did prefer their mother.
However, this preference was demonstrated only when pups were
tested with their siblings, but not when they were tested individ-
ually. The individually tested degus were still able to discriminate
between nest odors, and emitted more DVs in contact with their
home cage bedding (Fuchs et al., 2010), a nding reminiscent of
the restricted reunion effect described above (Bayart et al., 1990;
Colonnello et al., in press; Iacobucci et al., 2008; Wiener et al.,
1990). Insummary, infant degus showexibility intheir separation
responses at early developmental ages and in different experimen-
tal settings. In addition, infant degus have the capacity to recognize
their biological mother at roughly two weeks of age, although
they do not demonstrate this ability in every test setting. Likewise,
degu mothers are able to recognize their own offspring. Additional
researchwill needtoaddress thedevelopmental timecourse, speci-
city and persistence of social attachments between individuals of
varying age and relatedness in complex degu colonies.
4.2. Responses to chronic social isolation stress in early infancy
In humans, as in other mammals, proximity seeking to the care-
giver presumably serves as a modulator of infant emotional state
and the caretakers responses inuence the infants perception of
potential dangers inthe surrounding environment (Hay, 1980). As a
result, quality and quantity of parentinfant interactions inuence
aninfants emotional balancebetweentheneedfor proximitytothe
caregiver and the exploration of novel stimuli in the environment
(Ainsworth and Bell, 1970; Ainsworth et al., 1978). Thus, during
interactions with primary attachment gures, infants of strongly
bonded species exhibit specic attachment patterns (Ainsworth
et al., 1978; Suomi, 1999; Topl et al., 1998). Infants reared in
positive and responsive social environments are more inclined to
develop a secure attachment pattern and utilize the caregiver as
a secure base for the exploration of social and environmental
stimuli. By contrast, infants who have experienced certain forms
of physical and emotional neglect show a stronger risk of devel-
oping an insecure attachment pattern, which is associated with
altered levels of proximity seeking to the caregiver and exploratory
activity (Ainsworth and Bell, 1970; Suomi, 1999).
Accordingly, we investigated the long-term impact of differ-
ent levels of social contact on degu socio-emotional development.
Given that infant degus exposed to restricted interactions with
social partners show potentiated protest responses when unable
to obtain contact, perhaps reecting a frustration response aris-
ing from not being able to achieve a full reunion, we incorporated
a restricted contact condition in our study. To our knowledge, the
impact of repeated exposure to such conditions on infant devel-
opment has not previously been investigated in animal models of
social attachment.
Differences inapproachto novel social and environmental stim-
uli were observed in three groups of degus reared with varying
degrees of social contact. At 3 weeks of age, after the motherinfant
attachment bondwas presumablywell established, degupups were
placed in continuous isolation (ISOLATED group), kept in isolation
interrupted by daily 30-min restricted interactions with their fam-
ily members (mother and littermates) through a wire-mesh grid
(RESTRICTEDgroup), or housed socially with their family members
(SOCIAL group). After 10 days, all subjects were observed during a
single 10-minexposure toa novel environment, anddailyfor 5days
during a 10-min social choice test (mother vs unfamiliar female).
We found that, during the rst 3 days of the 10-day treatment
period, the RESTRICTED degus showed an elevated vocal protest
response (DVs) andsustainedproximityseekingtowards their fam-
ily during the entire 30-min restricted access period. By contrast,
the ISOLATED degus exhibited markedly decreased DVs and motor
Fig. 2. MeanSE % preference of young degu pups (n=16 per group, 8 males and 8
females) for their mother vs an unfamiliar female during the rst social choice test
after 10 days of continuous isolation (ISOLATED), isolation plus fenceline family
contact for 30-min daily (RESTRICTED) or continuous free access to family members
(SOCIAL). Data are presented in 5 blocks of 2min each (adapted from Colonnello
et al., in press). *p<0.05.
activity after 2 days of treatment. These animals settled in a pas-
sive crouching posture resembling the depression-like symptoms
observed in socially deprived human babies and non-human pri-
mates (Kaufman and Rosenblum, 1967; Spitz, 1946). Given that the
marked decrease of exploration in the ISOLATED degus could sim-
ply reect habituationto the isolationenvironment, further studies
are needed to assess whether the observed crouching posture is
accompanied by other depression-like responses in degus.
After the 10-day treatment period, when the animals were
placed individually in a novel environment, ISOLATED animals
showed increased locomotor activity and defecation, possibly
reecting escape attempts and thus a sustained increase in anx-
iety compared to the other groups (Colonnello et al., in press).
Differences among rearing conditions were also evident during
the social choice tests. In particular, during the rst choice test,
degus in the SOCIAL group spent more time close to their mother
only during the initial minutes of the test, resembling a secure
attachment pattern, while those in the RESTRICTEDgroup showed
persistent proximity seeking to their mother throughout the entire
test session, resembling human insecure attachment. Finally, the
ISOLATEDanimals spent a comparable amount of time close totheir
mother and the unfamiliar female, showing no social preference
(Fig. 2; Colonnello et al., in press).
In other words, different rearing conditions were associated
with different behavioral proles. Both groups reared under iso-
lation conditions showed forms of anxiety compared to animals
reared in continuous, full contact with their family members.
However, while degus in the ISOLATED group were neophobic
towards thenovel environment, perhaps RESTRICTEDanimals were
neophobic towards the unfamiliar female. No rearing conditiondif-
ferences were evident after the rst social test day, presumably
due to familiarizationwiththe environment andunfamiliar female.
Given that the pups were reared only by their mother and not in
communal nests with older siblings and other adults, it would be
of interest to take into account this aspect of the species-specic
biology of degus in future studies.
Basedonthe above observations, the deguexhibits considerable
promise as a valid animal model for the study of early infant attach-
ments. Degu infants showed persistent and exible attachment
behaviors during social separations. Moreover, infants discrimi-
natedandpreferredtheir mother over unfamiliar lactating females,
as monitored by choice tests (Colonnello et al., in press; Fuchs et al.,
2010). Infants remained in proximity to their mother at develop-
mental ages when they could eat solid food and their need for
maternal milk was greatly reduced, suggesting that their seek-
ing of proximity to the caregiver was not driven by a need for
nourishment per se but, rather, a direct expression of their social
V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863 1859
needs. Indeed, growth was not compromised in early-weaned
degus (Becker et al., 2007) or those placed in prolonged isolation at
PND 21 (Colonnello et al., in press). Furthermore, our nding that
psychological vulnerability was not limited to continuous social
isolation but was also observed at varying degrees of isolation
encourages the further study of the degu as a model for human
attachments. Prima facie, the distinct behavioral proles observed
in isolated degus resemble human secure and insecure attach-
ment patterns. It is noteworthy that just as in our own species,
in which young children try to maintain a close bond even with
neglectful caregivers (Cicchetti andToth, 1995), young RESTRICTED
degus tried to reach their social group even after several days of
thwarted access, which was presumably a very unsatisfying state
of affairs. Thus, the urge to maintain a social bond in degus is strong
and enduring, regardless of the quality of the social interactions.
Future studies may elucidate the specic factors inuencing the
formation and persistence of parentinfant bonding in this species.
Inparticular, weneedtodeterminetheroleof motheringcalls and
infant reunion calls in facilitating parentinfant recognition and
bonding. Whether such calls are modulated by social rearing con-
ditions is another key question that needs to be addressed. Along
these lines, it is worth noting that in another precocial species,
the domestic pig, infants modulate the number of reunion calls
based on the time spent away from the family group and the qual-
ity of interactions with the caregiver (Colonnello et al., 2010). Our
ongoing research is currently focused on the long-term effects of
social isolation on emotional development of degus isolated since
the second week of life. The current pattern of results afrms that
the degu is a ne species for studying the neurobiology of attach-
ment bonds. The data also suggest that this species may be used
to model insecure attachment patterns, which is a major topic in
human attachment research, but for which no small animal model
yet exists.
5. Peer interactions and their role on socio-emotional
development in juvenile degus
The protracted period of infancy and adolescence spent in the
natal colony allows young degus to interact with siblings and non-
siblings for a considerable period of time before they disperse or
become fully integrated adult colony members. Thus, we have been
interested in investigating the characteristics of social peer inter-
actions and their role throughout development.
5.1. Peer interactions in juvenile degus
Studies on peer play activity have demonstrated that, in most
social mammals, an urge for rough-and-tumble play emerges in
early stages of life, peaks during the juvenile period, and declines
at puberty (Panksepp, 1998; Pellis and Pellis, 2007). It is, thus, to
be expected that social play is an experience expectant process
in all mammals, which helps construct and solidify the social skills
needed later in life. Considerable progress has been made in under-
standing the brain mechanisms that regulate play in juvenile rats
(Siviy, in this issue). To see how well future research on play pro-
cesses could be pursued in another convenient laboratory species,
we proceeded to characterize the expression and developmental
patterns of play in young degus. Contrast between rats and degus
may be especially interesting since the former are born altricial,
and the latter, precocious.
Thanks to their well-developed sensory and motor abilities at
birth, young degus have substantive social exchanges with their
siblings from the rst days of life. By the second postnatal week,
degus show coordinated episodes of rough-and-tumble play, in
which they alternate their dominance-submission roles. The play-
ful behaviors observed are dorsal contacts (paw contact with the
dorsal surface of the play partner), riding (the play partner is
mounted from behind, then the pair starts to run forward) and
foreleg push (both partners face each other on their hind legs
and pawat each other with their forelegs, a behavior that precedes
more serious forms of ghting in adults; for an earlier account on
degu play see Wilson and Kleiman, 1974). All of these behaviors
are accompanied by play vocalizations, which have been char-
acterized as warbles (Long, 2007), and closely resemble friendly
vocalizations emitted by adults (Braun and Scheich, 1997) as well
as the mothering call emitted by nursing females.
Play is clearly a major emotional urge in young degus. Indeed,
2-week-old degus show a play rebound effect when reunited
following 12h of isolation (Fuchs et al., in preparation), an effect
similar to that reported in rats (Holloway and Suter, 2004;
Panksepp et al., 1984). Through focal observations of degus in their
family groups during the rst three weeks after birth, Pinkernelle
et al. (2009) reported that pups decreased their play activity in the
third week of life. By contrast, in young degus reared without their
father and observed in the absence of adults, we found that sibling
play activity continued for the rst 6 weeks of life at comparable
levels (Fuchs et al., in preparation). Possibly, the inhibitory role of
older family members (Wilson, 1982) accounts for the differences
between ndings. Whether play activity in degus persists for a suf-
ciently long developmental windowas to promote complex social
organization in this species awaits further investigation.
5.2. Effects of deprivation of peer interactions during the play
period
In light of their motivation for social attachment and play, it
is not surprising that deprivation of peer interactions for a pro-
longed period has negative effects on young degu emotional and
social development. To evaluate the potential utility of this model,
we observed the developmental trajectories of young degus that
werechronicallyisolated(CHRONICISOLATIONgroup), isolatedbut
allowed to interact freely with a sibling for 1h daily (PARTIAL ISO-
LATION group), or reared with continuous free access to a sibling
(SOCIAL group) starting on PND 25 (Colonnello et al., 2011).
After two weeks, chronically isolated degus, but not those
allowed 1h of interaction daily, showed maturational delay of fear
responses, failing to show freezing behavior in response to unex-
pected loud noises. After two more weeks of isolation, chronically
isolated animals exhibited impaired fear responses and increased
risk-taking behaviors during the exploration of novel environ-
ments, as measured during open eld and novelty tests. The
chronic isolation stress also promoted the consumption of palat-
able sucrose solution, as monitored in a sucrose preference test
in which the alternative was plain water. Other effects of social
isolation were observed in the social domain: both isolated and
partially isolated animals emitted fewer warble vocalizations dur-
inginteractions withunfamiliar social partners thananimals reared
socially. A diet of intermittent social peer interactions (reunions
for 1h each day) attenuated the effects of isolation and aided the
development of fear and inhibitory responses. However, only the
continuous availability of peers promoted a functional develop-
ment of social abilities (Table 1; Colonnello et al., 2011), suggesting
a dissociation between the maturation of fear-related responses
and social skills in this species.
In sum, during the juvenile period, the deprivation of social peer
interactions impairs the development of adaptive fear responses,
and qualitative aspects of social behavior, in degus. In humans,
the regulation of emotional abilities typically develops along with
the maturation of frontal lobe inhibitory functions. However, chil-
dren with externalizing problems are more likely to showimpaired
frontal lobe regulatory functions, difculty in regulating their emo-
1860 V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863
Table 1
MeanSE % sucrose preference, and frequencies of central crosses in an Open Field test (n/5min), entries to a novel area in a Novelty test (n/20min), and warble vocalizations
during a Sociability test (n/20min). Data refer to the responses of 52-day-old degus (n=16 per group, 8 males, 8 females) tested after 4 weeks of chronic isolation (CHRONIC
ISOLATION), isolation in conjunction with free access to a sibling for 1h daily (PARTIAL ISOLATION), or continuous free access to a sibling (SOCIAL) (adapted from Colonnello
et al., 2011).
Rearing condition Test and relative response
Sucrose
% Sucrose preference
Open eld
Freq. central crosses
Novelty
Freq. entries novel area
Sociability
Freq. approach vocalizations
CHRONIC ISOLATION 98 1
*
9 1
*
20 2
*
12 2
PARTIAL ISOLATION 83 4 6 1 10 2 9 3
SOCIAL 82 5 6 1 9 2 39 11
*
*
p<0.05.
tions, and impaired social communication skills. They showaltered
reward processing, decient inhibition, and impaired performance
in task-set shifting (Romer et al., 2009; Rubia et al., 2007; Sonuga-
Barke et al., 2008; Tsujimoto, 2008) as found, in part, in our
chronically isolated degus. It is noteworthy that, contrary to rat
models of depression, in which such stressors generally decrease
sucrose consumption, isolated degus exhibited elevated consump-
tion.
In children, friendly peer exchanges generally promote social
development and counteract the emergence of externalizing
behaviors (Witvliet et al., 2009). Likewise, positive peer interac-
tions arising from modest social play opportunities (i.e., when
reunited for 1h daily) appeared to counteract the kinds of behav-
ioral decits produced by isolation in degus. Thus, our results
support the hypothesis that availability of playful peer interac-
tions may facilitate the development of emotional regulation and
social abilities (Gordonet al., 2003; Pankseppet al., 2003; Panksepp,
2007).
These behavioral ndings are propaedeutic for further valida-
tion of this animal model of human externalizing disorders during
early childhood and suggest other inquiries about protective fac-
tors for emotional and behavioral disorders that are common in
humans. Future research should focus on the ontogeny of impulse
control problems and how peer interactions aid emotional reg-
ulation, as developmentally evaluated in degus reared in more
naturalistic environments (e.g., with both parents, older siblings,
and non-siblings). Evaluation of impulsivity, in its various forms of
disinhibition (i.e., inability to inhibit ongoing response) including
delay aversion in children (i.e., marked preference for immediate
rewards over delayed, but greater, rewards), could be performed
in degus deprived of peer social play at different developmental
stages. Such impulsivity seems to be a core behavior in external-
izing disorders and may be evident during approach to various
environmental stimuli as well as during social interactions.
In addition, overactivity, another main feature found in exter-
nalizing disorders, should be systematically investigated in both
familiar and unfamiliar environments. For instance, our chroni-
callyisolatedjuvenile degus exhibitednooveractivity(measuredas
overall motor locomotor activity) during the open eld and novelty
tests. In other words, the isolated group showed an increased pref-
erence for entering the center of the open eld without any overall
increased motor or locomotor activity. However, overactive chil-
dren may showrestlessness and overactivity selectively in familiar
contexts (Sagvolden et al., 1998).
5.3. Effects of deprivation of peer interactions since early
adolescence
We have found that social isolation since early adolescence
induces anemotional prole resembling some symptoms of human
anxiety disorders, indicating that peer interactions serve an impor-
tant role beyondthe playperiodindegus. We contrastedbehavioral
proles of 8 female degus housed socially and 8 females that were
isolate-housed at PND 45. When tested four months later, the
isolated degus showed altered responses in emotional tests com-
pared to socially housed degus (Colonnello et al., submitted for
publication). Specically, the isolated females again expressed an
increased hedonic response in a sucrose preference test, increased
anxiety during an open eld test, and an initial freezing response
in conjunction with diminished exploration when exposed to a
novel environment. Of course, no one has demonstrated reduced
intake of sweets in depressed humans. Instead, the response to
stress is often associated with increased intake of sweets in chil-
dren (Mennella et al., 2010) as well as in adults (Oliver et al.,
2000). Thus, we should leave open which is the more human-
characteristic response andproceedwitha more critical andcareful
conceptualization of human anhedonic responses to develop valu-
able preclinical models of depression.
Intriguingly, the isolated degus also showed a freezing response
when exposed to a lost pup (outside the nest) in a familiar envi-
ronment, and a longer latency to approach the pup than socially
housed individuals, suggestive of neophobia. Additionally or alter-
natively, perhaps the isolated degus perceived the infant emotional
state as aversive, and were unable to regulate their emotions and
exhibit prosocial behaviors. Given that, under natural conditions,
adults participate in alloparenting of younger siblings and non-
siblings, and pup survival may be dependent on the cooperation
and prosocial behavior of all group members, the above-noted de-
ciency in responsiveness to pups highlights how living in social
isolation could impair social tness in degus.
Similarly, whereas human parents and other adults naturally
direct caretaking behavior towards lost infants, individuals with
highanxietylevels andexperiences of social exclusionshowaltered
responsiveness to infant signals (Burchinal et al., 1996; Glocker
et al., 2009; Kringelbach et al., 2008; Nicol-Harper et al., 2007).
Social isolation and unsatisfying peer relationships during adoles-
cence also increase anxiety, especially when confronted by novelty
(Chartier et al., 1998), which may promote depression later in life
(Hankinet al., 2007; Larsonet al., 1990). Along traditionof research
has focused on effects of early maternal care on future parent-
ing ability of offspring. However, decient relationships with the
infant, such as in post-partum depression, can also be found in
women who have experienced positive interactions with parents
during childhood, but lack social support during later stages of life
(Robertson et al., 2004). To assess the validity of degus for mod-
eling these processes, future studies on degus should investigate
whether high anxiety levels due to post-weaning social isolation
persist after re-socialization experiences and parenthood.
6. Methodological considerations
Some methodological considerations should be taken into
account when usingdegus in laboratory settings. The rst concerns
the long gestationperiod(Lee, 2004) which, onone hand, may facil-
itate the study of prenatal development and emotional changes in
V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863 1861
pregnant females duringthedifferent gestational phases but, onthe
other hand, adds to the cost of colony maintenance and prolongs
intergenerational studies. Secondly, due to strong social prefer-
ences and aversions, adult degus have to be monitored closely
for potentially fatal ghting when rst introduced. Thirdly, when
adults are kept in malefemale pairs, it may be necessary to limit
the number of new litters produced. In our studies, we separated
the male from the female before the pups were born to prevent
postpartumpregnancies, but paternal deprivationearlyinlifecould
inuence the social emotional development of the young.
In this context, it is noteworthy that in our studies, infant male
degus showed stronger protest responses to isolation than infant
females (Colonnello et al., in press). However, we found an over-
all lack of sex differences in juvenile degus observed during the
play period, regardless of their rearing condition (Colonnello et al.,
2011). Whether this lack of sex difference was inuenced by the
absence of the father is unknown. Several studies suggest that the
father may play a crucial role in the early neurodevelopment of off-
spring (Helmeke et al., 2009; Pinkernelle et al., 2009), but not in
perinatal survival rates (Ebensperger et al., 2010). Thus, the behav-
ioral characterization of possible sex differences in vulnerability
and resilience of degus reared in different family structures would
be relevant for further validation of this promising animal model.
These studies would be especially relevant considering that, in
humans, sex-related differences in the onset and manifestation of
emotional disorders emerge inearly childhood(Dekker et al., 2007;
Zahn-Waxler et al., 2008).
As for other animal models, behavioral assessment should take
species-specic characteristics into account. Under natural condi-
tions, degus run fromone burrowto another and travel across open
areas during the day (Ebensperger and Bozinovic, 2000). Therefore,
studies including the openeldtest andother tests aimedat assess-
ing fear responses should be developed using suitable protocols.
For example, the use of a regular 70cm70cm70cm (relatively
small) openeld arena might mask behavioral differences between
isolated and socially housed young degus in classic measures of
anxiety (Braun et al., 2003; Cloutier et al., in preparation). In addi-
tion, because degus are visually perceptive in the ultraviolet range
(Chavez et al., 2003; Quirici et al., 2008), visual cues should be care-
fully controlled according to experimental goals. Finally, particular
attention should be also paid to sucrose concentrations in pref-
erence tests and conditioning using palatable food due to a great
vulnerability to diabetes mellitus of this species.
7. Conclusions
O. degus is an animal model offering fruitful new opportu-
nities for investigating the environmental and neural processes
underlying human social affectional bonds and their role in emo-
tional development later in life. Degus also offer a potentially
useful model for the study of human psychopathologies, including
ADHD, depression and anxiety disorders. Social deprivation, which
is a widely acknowledged risk factor for human psychopathol-
ogy, induces a series of species-atypical behaviors in degus. In
humans, social deprivation has distinct age-specic effects. Like-
wise, in degus, a disruption of the social environment may have
different effects during successive developmental windows.
During infancy, chronic isolation or restricted interactions with
primary caregivers and other available social partners inuence
degusocial skills negatively andimpair motivationto explore novel
stimuli, as in human infants. During the phase of high juvenile
play, diminished availability of peer interactions increases the like-
lihoodof risk-taking behaviors andalterationof rewardprocessing,
which are behavioral alterations similar to some of the symptoms
found in children with ADHD and other externalizing disorders.
Furthermore, chronic isolation during adolescence increases the
risk for emergence of atypical behaviors resembling the symptoms
of human anxiety and depressive disorders. Thus, this pre-clinical
model seems likely to satisfy causative and face validity criteria.
Our ndings so far also provide optimismthat degu models ful-
ll predictive validity criteria for the positive inuences of early
social stimulation in promoting resilience to future stressors. As
demonstrated by the ne work of Brauns group, exposure to select
social stimuli can offer valuable neurodevelopmental support, at
both behavioral and neurophysiological levels, for recovering from
ongoing and previous stressful experience (Ziabreva et al., 2000,
2003). We note that the predictive validity of animal models is
typically assessed by observing animal therapeutic responses to
pharmacological agents. However, we initially decided to observe
theresponses toatreatment basedonrepeatedexposures toposi-
tive social exchanges. We opted for this validation method because
we wished to focus on a developmental period corresponding to
human late childhood, during which pharmacological treatments
may not be desirable due to unknown neurodevelopmental effects.
Our ndings indicate that the availability of peer exchanges for just
an hour a day mitigates the effects of social isolation and induces a
phenotype that is more similar to socially housed animals than iso-
late housed ones. Likewise, in humans, social support is considered
among the most protective factors, exerting positive effects during
stressful negative life events (Ozbay et al., 2008; Silk et al., 2007).
The development of an ideal animal model that meets the
construct validitycriterionis particularlydifcult. Humanexternal-
izing and internalizing disorders are complex and heterogeneous
conditions that cannot yet be attributedto specic brainalterations
or exclusively to specic genetic susceptibility factors. However,
for a promising attempt to validate this pre-clinical model, we
again turn to the ndings of Brauns group. These investigators
have foundthat changes inbalance of serotoninergic anddopamine
innervations in early socially isolated degus resemble the brain
changes found in humans exposed to early adverse social expe-
riences (Ovtscharoff and Braun, 2001; Zehle et al., 2007).
We conclude that O. degus appears to be a suitable model for
advancing knowledge on the emergence of human psychopathol-
ogy across the life span. These creatures may supplement the ne
work being done onadult pair bonding inprairie voles witha model
for developmental attachment dynamics, in well controlled ways
that may not be possible with altricial species.
Acknowledgements
This research was supported by a Hope for Depression Research
Foundation grant to J.P.
References
Ainsworth, M.D.S., Bell, S.M., 1970. Attachment, exploration, and separation: illus-
trated by the behavior of one-year-olds in a strange situation. Child Dev. 41,
4967.
Ainsworth, M.D.S., Blehar, M.C., Waters, E., Wall, S., 1978. Patterns of Attachment:
A Psychological Study of the Strange Situation. Lawrence Erlbaum Associates,
Hillsdale, NJ.
Aragona, B.J., Wang, Z., 2004. The prairie vole (Microtus ochrogaster): an animal
model for behavioral neuroendocrineresearchonpair bonding. ILARJ. 45, 3545.
Bayart, F., Hayashi, K.T., Faull, K.F., Barchas, J.D., Levine, S., 1990. Inuence of mater-
nal proximity on behavioral and physiological responses to separation in infant
rhesus monkeys (Macaca mulatta). Behav. Neurosci. 104, 98107.
Becker, K., Abraham, A., Kindler, J., Helmeke, C., Braun, K., 2007. Exposure to neonatal
separation stress alters exploratory behavior and corticotropin releasing factor
expression in neurons in the amygdale and hippocampus. Dev. Neurobiol. 67,
617629.
Blanchard, D.C., Griebel, G., Blanchard, R.J., 2001. Mouse defensive behaviors: phar-
macological and behavioral assays for anxiety and panic. Neurosci. Biobehav.
Rev. 25, 205218.
Bowlby, J., 1969. Attachment and Loss: Vol. 1. Attachment. Basic Books, New York.
Braun, S., Scheich, H., 1996. Inuence of experience on the representation of the
mothering call in auditory and other cortices of pups of the rodent Octodon
degus: a FDG mapping study. J. Comp. Physiol. A 181, 697709.
1862 V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863
Braun, S., Scheich, H., 1997. Inuence of experience on the representation of the
mothering call in frontoparietal and auditory cortex of pups of the rodent
Octodon degus: FDG mapping. J. Comp. Physiol. A 181, 697709.
Braun, K., Lange, E., Metzger, M., Poeggel, G., 2000. Maternal separation followed
by early social deprivation affects the development of monoaminergic ber
systems in the medial prefrontal cortex of Octodon degus. Neuroscience 95,
309318.
Braun, K., Kremz, P., Wetzel, W., Wagner, T., Poeggel, G., 2003. Inuence of parental
deprivation on the behavioral development in Octodon degus: modulation by
maternal vocalizations. Dev. Psychobiol. 42, 237245.
Burchinal, M.R., Follmera, A., Bryant, D.M., 1996. The relations of maternal social
support and family structure with maternal responsiveness and child outcomes
among African American families. Dev. Psychol. 32, 10731083.
Carter, C.S., Getz, L.L., 1993. Monogamy and the prairie vole. Sci. Am. 268, 100106.
Cassidy, J., 1999. The nature of the childs ties. In: Cassidy, J., Shaver, P.R. (Eds.),
Handbook of Attachment: Theory, Research, and Clinical Applications. Guilford
Press, New York, pp. 320.
Chavez, A.E., Bozinovic, F., Peichl, L., Palacios, A.G., 2003. Retinal spectral
sensitivity, fur coloration, and urine reectance in the genus Octodon
(Rodentia): implications for visual ecology. Invest. Ophthalmol. Vis. Sci. 44,
22902296.
Chartier, M.J., Hazen, A.L., Stein, M.B., 1998. Lifetime patterns of social phobia: a
retrospective study of the course of social phobia in a nonclinical population.
Depress. Anxiety 7, 113121.
Cicchetti, D., Toth, S.L., 1995. Adevelopmental psychopathology perspective onchild
abuse and neglect. J. Am. Acad. Child Psychiatry 34, 541565.
Cicchetti, D., Rogosch, F.A., Sturge-Apple, M.L., 2007. Interactions of child maltreat-
ment and serotonin transporter and monoamine oxidase A polymorphisms:
depressive symptomatology among adolescents fromlowsocioeconomic status
backgrounds. Dev. Psychopathol. 19, 11611180.
Colonnello, V., Iacobucci, P., Newberry, R.C., 2010. Vocal and locomotor responses of
piglets to social isolation and reunion. Dev. Psychobiol. 52, 112.
Colonnello, V., Iacobucci, P., Panksepp, J. Analysis of the disruptionof maternal social
bonds in Octodon degus: separation distress in restricted reunion tests. Dev.
Psychobiol., doi:10.1002/dev.20539.
Colonnello, V., Iacobucci, P., Anderson, M.P., Panksepp, J., 2011. Brief periods of
positive peer interactions mitigate the effects of total social isolation in young
Octodon degus. Dev. Psychobiol. 53, 280290.
Colonnello, V., Newberry, R.C., Panksepp, J. Octodon degus as a novel pre-clinical
model for social isolation promoting anxiety and depressive responses, submit-
ted for publication.
Dekker, M.C., Ferdinand, R.F., van Lang, N.D., Bongers, I.L., van der Ende, J., Verhulst,
F.C., 2007. Developmental trajectories of depressive symptoms fromearly child-
hoodtolate adolescence: gender differences andadult outcome. J. ChildPsychol.
Psychiatry 48, 657666.
Ebensperger, L.A., 2001. No infanticide in the hystricognath rodent, Octodon degus:
does ecology play a role? Acta Ethol. 3, 8993.
Ebensperger, L.A., Bozinovic, F., 2000. Communal burrowing in the hystricognath
rodent, Octodon degus: a benet of sociality? Behav. Ecol. Sociobiol. 47, 365369.
Ebensperger, L.A., Veloso, C., Wallem, P.K., 2002. Do female degus communally nest
and nurse their pups? J. Ethol. 20, 143146.
Ebensperger, L.A., Hurtado, M.J., Soto-Gamboa, M., Lacey, E.A., Chang, A.T., 2004.
Communal nesting and kinship in degus (Octodon degus). Naturwissenschaften
91, 391395.
Ebensperger, L.A., Hurtado, M.J., Valdivia, I., 2006. Lactating females do not discrimi-
nate between their own young and unrelated pups in the communally breeding
rodent, Octodon degus. Ethology 112, 921929.
Ebensperger, L.A., Hurtado, M.J., Len, C., 2007. An experimental examination of the
consequences of communal versus solitary breeding on maternal condition and
the early postnatal growth and survival of degu, Octodon degus, pups. Anim.
Behav. 73, 185194.
Ebensperger, L.A., Ramrez-Otarola, N., Len, C., Ortiz, M.E., Croxatto, H.B., 2010.
Early tness consequences and hormonal correlates of parental behaviour in
the social rodent, Octodon degus. Physiol. Behav. 101, 509517.
Fox, W.M., 1965. Reex-ontogenyandbehavioural development of themouse. Anim.
Behav. 13, 234241.
Fuchs, T., Iacobucci, P., MacKinnon, K., Panksepp, J., 2010. Infantmother recognition
in a social rodent (Octodon degus). J. Comp. Psychol. 124, 166175.
Fulk, G.W., 1976. Notes on the activity, reproduction, and social behavior of Octodon
degus. J. Mammal. 57, 495505.
Geyer, L.A., 1981. Ontogeny of ultrasonic and locomotor responses to nest odors in
rodents. Am. Zool. 21, 117128.
Glaser, D., 2000. Child abuse and neglect and the brain: a review. J. Child Psychol.
Psychiatry 41, 97116.
Glocker, M.L., Langleben, D.D., Ruparel, K., Loughead, J.W., Valdez, J.N., Grifn, M.D.,
Sachser, N., Gur, R.C., 2009. Baby schema modulates the brain reward system in
nulliparous women. Proc. Natl. Acad. Sci. U.S.A. 106, 91159119.
Gordon, N.S., Burke, S., Akil, H., Watson, S.J., Panksepp, J., 2003. Socially inducedbrain
fertilization: play promotes brain derived neurotrophic factor transcription in
the amygdala and dorsolateral frontal cortex in juvenile rats. Neurosci. Lett. 341,
1720.
Hankin, B.L., Mermelstein, R., Roesch, L., 2007. Sex differences in adolescent depres-
sion: stress exposure and reactivity models. Child Dev. 78, 279295.
Harlow, H.F., Zimmermann, R.R., 1959. Affectional responses in the infant mon-
key; orphaned baby monkeys develop a strong and persistent attachment to
inanimate surrogate mothers. Science 130, 421432.
Hay, D.F., 1980. Multiple functions of proximity seeking in infancy. Child Dev. 51,
636645.
Hayes, L.D., Chesh, A.S., Castro, R.A., Tolhuysen, L.O., Burger, J.R., Bhattacharjee,
J., Ebensperger, L.A., 2009. Fitness consequences of group living in the degu
Octodon degus, a plural breeder rodent with communal care. Anim. Behav. 78,
131139.
Helmeke, C., Ovtscharoff Jr., W., Poeggel, G., Braun, K., 2001. Juvenileemotional expe-
rience alters synaptic inputs on pyramidal neurons in the anterior cingulate
cortex. Cereb. Cortex 11, 717727.
Helmeke, C., Ovtscharoff Jr., W., Poeggel, G., Braun, K., 2008. Imbalance of immuno-
histochemically characterized interneuron populations in the adolescent and
adult rodent medial prefrontal cortex after repeated exposure to neonatal sep-
aration stress. Neuroscience 152, 1828.
Helmeke, C., Seidel, K., Poeggel, G., Bredy, T.W., Abraham, A., Braun, K., 2009. Pater-
nal deprivation during infancy results in dendrite- and time-specic changes of
dendritic development and spine formation in the orbitofrontal cortex of the
biparental rodent Octodon degus. Neuroscience 163, 790798.
Hennessy, M.B., Miller, E.E., Shair, H.N., 2006. Brief exposure to the biological mother
potentiates the isolation behavior of precocial Guinea pig pups. Dev. Psy-
chobiol. 48, 653659.
Holloway, K.S., Suter, R.B., 2004. Play deprivation without social isolation: housing
controls. Dev. Psychobiol. 44, 5867.
Hrdy, S.B., 2009. Mothers and Others. The Belknap Press of Harvard University Press,
Cambridge, MA.
Iacobucci, P., Colonnello, V., Newberry, R.C., 2008. Piglets call for mothers attention:
piglet attachment vocal responses are modulated by proximity to their mother.
In: Proc. 41st Annual Meeting of the International Society for Developmental
Psychobiology , November 1215, 2008, Washington, DC.
Jesseau, S.A., Holmes, W.G., Lee, T.M., 2008. Motheroffspring recognition in com-
munally nesting degus, Octodon degus. Anim. Behav. 75, 573582.
Jesseau, S.A., Holmes, W.G., Lee, T.M., 2009. Communal nesting and discriminative
nursing by captive degus, Octodon degus. Anim. Behav. 78, 11831188.
Illmann, G., Schrader, L.,

Spinka, M.,

Sustr, P., 2002. Acoustical motheroffspring
recognition in pigs (Sus scrofa domesticus). Behaviour 139, 487505.
Jamon, M., 2006. The earlydevelopment of motor control inneonate rat. C. R. Palevol.
5, 657666.
Jezierski, G., Braun, K., Gruss, M., 2006. Epigenetic modulation of the developing
serotonergic neurotransmission in the semi-precocial rodent Octodon degus.
Neurochem. Int. 48, 350357.
Kalin, N.H., Shelton, S.E., Lynn, D.E., 1995. Opiate systems in mother and infant pri-
mates coordinate intimate contact during reunion. Psychoneuroendocrinology
20, 735742.
Kaufman, J.C., Rosenblum, L.A., 1967. The reaction to separation in infant mon-
keys: anaclitic depression and conservation withdrawal. Psychosom. Med. 29,
748675.
Kaufman, J., Yang, B., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D., Krystal, J.H.,
Gelernter, J., 2004. Social supports and serotonin transporter gene moderate
depressioninmaltreatedchildren. Proc. Natl. Acad. Sci. U.S.A. 101, 1731617321.
Kringelbach, M.L., Lehtonen, A., Squire, S., Harvey, A.G., Craske, M.G., Holliday, I.E.,
Green, A.L., Aziz, T.Z., Hansen, P.C., Cornelissen, P.L., Stein, A., 2008. A specic
and rapid neural signature for parental instinct. PLoS One 3, e1664.
Larson, R.W., Raffaelli, M., Richards, M.H., Ham, M., Jewell, L., 1990. Ecology of
depression in late childhood and early adolescence: a prole of daily states and
activities. J. Abnorm. Psychol. 99, 92102.
Lee, T.M., 2004. Octodon degus: a diurnal, social, and long-lived rodent. ILAR J. 45,
1424.
Legerstee, M., Markova, G., 2007. Intentions make a difference: infant responses to
still-face and modied still-face conditions. Infant Behav. Dev. 30, 232250.
Long, C.V., 2007. Vocalisations of thedeguOctodondegus, asocial caviomorphrodent.
Bioacoustics 16, 223244.
MacLean, P., 1985. Brain evolution relating to family, play and separation call. Arch.
Gen. Psychiatry 42, 405417.
MacLean, P.D., 1990. The Triune Brain in Evolution: Role in Paleocerebral Functions.
Plenum Press, New York.
Mennella, J.A., Pepino, M.Y., Lehmann-Castor, S.M., Yourshaw, L.M., 2010. Sweet
preferences and analgesia during childhood: effects of family history of alco-
holism and depression. Addiction 105, 666675.
McKinney, W.T., Bunney, W.E., 1969. Animal models of depression: review of evi-
dence and implications for research. Arch. Gen. Psychiatry 21, 240248.
Nicol-Harper, R., Harvey, A.G., Stein, A., 2007. Interactions between mothers and
infants: impact of maternal anxiety. Infant Behav. Dev. 30, 161167.
Oliver, G., Wardle, J., Gibson, E.L., 2000. Stress and food choice: a laboratory study.
Psychosom. Med. 62, 853865.
Ovtscharoff Jr., W., Braun, K., 2001. Maternal separation and social isolation modu-
late the postnatal development of synaptic compositioninthe infralimbic cortex
of Octodon degus. Neuroscience 104, 3340.
Ozbay, F., Fitterling, H., Charney, D., Southwick, S., 2008. Social support andresilience
to stress across the life span: a neurobiologic framework. Curr. Psychiatry Rep.
10, 304310.
Panksepp, J., 1982. Toward a general psychobiological theory of emotions. Behav.
Brain Sci. 5, 407467.
Panksepp, J., Herman, B., Conner, R., Bishop, P., Scott, J.P., 1978. The biology of
social attachments: opiates alleviate separation distress. Biol. Psychiatry 9,
213220.
Panksepp, J., Siviy, S., Normansell, L., 1984. The psychobiology of play: theoretical
and methodological perspectives. Neurosci. Biobehav. Rev. 8, 465492.
V. Colonnello et al. / Neuroscience and Biobehavioral Reviews 35 (2011) 18541863 1863
Panksepp, J., Newman, J.D., Insel, T.R., 1992. Critical conceptual issues in the analysis
of separation-distress systems of the brain. In: Strongman, K.T. (Ed.), Interna-
tional Review of Studies on Emotion, vol. 2. Wiley, New York, pp. 5172.
Panksepp, J., 1998. Affective Neuroscience: The Foundations of Human and Animal
Emotions. Oxford University Press, New York.
Panksepp, J., 2003. Can anthropomorphic analyses of separation cries in other ani-
mals inform us about the emotional nature of social loss in humans? Comment
on Blumberg and Sokoloff (2001). Psychol. Rev. 110, 376388.
Panksepp, J., Burgdorf, J., Turner, C., Gordon, N., 2003. Modeling ADHD-type arousal
with unilateral frontal cortex damage in rats and benecial effects of play ther-
apy. Brain Cogn. 52, 97105.
Panksepp, J., 2005. Affective consciousness: core emotional feelings in animals and
humans. Conscious. Cogn. 14, 1969.
Panksepp, J., 2007. Can PLAY diminish ADHD and facilitate the construction of the
social brain? J. Can. Acad. Child Adolesc. Psychiatry 16, 5766.
Pellis, S.M., Pellis, V.C., 2007. Rough-and-tumble play and the development of the
social brain. Curr. Dir. Psychol. Sci. 16, 9598.
Pinkernelle, J., Abraham, A., Seidel, K., Braun, K., 2009. Paternal deprivation induces
dendritic and synaptic changes and hemispheric asymmetry of pyramidal neu-
rons in the somatosensory cortex. Dev. Neurobiol. 69, 663673.
Poeggel, G., Lange, E., Hase, C., Metzger, M., Gulyaeva, N., Braun, K., 1999. Mater-
nal separation and early social deprivation in Octodon degus: quantitative
changes of nicotinamide adenine dinucleotide phosphate-diaphorase-reactive
neurons in the prefrontal cortex and nucleus accumbens. Neuroscience 94,
497504.
Poeggel, G., Nowicki, L., Braun, K., 2003. Early social deprivation alters monoamin-
ergic afferents in the orbital prefrontal cortex of Octodon degus. Neuroscience
116, 617620.
Quirici, V., Castro, R.A., Oyarzun, J., Ebensperger, L.A., 2008. Female degus (Octodon
degus) monitor their environment while foraging socially. Anim. Cogn. 11,
441448.
Quirici, V., Faugeron, S., Hayes, L.D., Ebensperger, L.A., 2010. The inuence of group
size on natal dispersal in the communally rearing and semifossorial rodent,
Octodon degus. Behav. Ecol. Sociobiol., doi:10.1007/s00265-010-1082-1.
Redei, E.E., Ahmadiyeh, N., Baum, A.E., Sasso, D.A., Slone, J.L., Solberg, L.C., Will,
C.C., Volenec, A., 2001. Novel animal models of affective disorders. Semin. Clin.
Neuropsychiatry 6, 4367.
Reynolds, T.J., Wright, J.W., 1979. Early postnatal physical and behavioural develop-
ment of degus (Octodon degus). Lab. Anim. (Lond.) 13, 9399.
Robertson, E., Grace, S., Wallington, T., Stewart, D.E., 2004. Antenatal risk factors for
postpartum depression: a synthesis of recent literature. Gen. Hosp. Psychiatry
26, 289295.
Romer, D., Betancourt, L., Giannetta, J.M., Brodsky, N.L., Farah, M., Hurt, H., 2009.
Executive cognitive functions and impulsivity as correlates of risk taking and
problem behavior in preadolescents. Neuropsychologia 47, 29162926.
Roush, R.S., Snowdon, C.T., 2001. Food transfer and development of feeding behav-
ior and food-associated vocalizations in Cotton-top tamarins. Ethology 107,
415429.
Rubia, K., Smith, A., Taylor, E., 2007. Performance of children with Attention Decit
Hyperactivity Disorder (ADHD) on a test battery of impulsiveness. Child Neu-
ropsychol. (Neuropsychol. Dev. Cognition C) 13, 276304.
Sagvolden, T., Aase, H., Zeiner, P., Berger, D.F., 1998. Altered reinforcement mecha-
nisms in attention-decit/hyperactivity disorder. Behav. Brain Res. 94, 6171.
Shair, H.N., 2007. Acquisition and expression of a socially mediated separation
response. Behav. Brain Res. 182, 180192.
Silk, J.S., Vanderbilt-Adriance, E., Shaw, D.S., Forbes, E.E., Whalen, D.J., Ryan, N.D.,
Dahl, R.E., 2007. Resilience among children and adolescents at risk for depres-
sion: mediationandmoderationacross social andneurobiological contexts. Dev.
Psychopathol. 19, 841865.
Sonuga-Barke, E.J.S., Sergeant, J.A., Nigg, J., Willcutt, E., 2008. Executive dysfunction
and delay aversion in Attention Decit Hyperactivity Disorder: nosologic and
diagnostic implications. Child Adolesc. Psychiatr. Clin. N. Am. 17, 367384.
Soto-Gamboa, M., Villaln, M., Bozinovic, F., 2005. Social cues and hormone levels in
male Octodon degus (Rodentia): a eld test of the challenge hypothesis. Horm.
Behav. 47, 311318.
Spitz, R.A., 1946. Anaclitic depression. Psychoanal. Study Child 2, 313347.
Suomi, S.J., 1999. Attachment in rhesus monkeys. In: Cassidy, J., Shaver, P.R. (Eds.),
Handbook of Attachment: Theory, Research, and Clinical Applications. Guilford
Press, New York, pp. 320.
Topl, J., Miklsi, A., Csnyi, V., Dka, A., 1998. Attachment behavior in dogs (Canis
familiaris): a new application of Ainsworths (1969) Strange Situation Test. J.
Comp. Psychol. 112, 219229.
Tronick, E.Z., Adamson, L., Wise, S., Brazelton, T.B., 1978. The infants response to
entrapment between contradictory messages in face to face interaction. J. Am.
Acad. Child Psychiatry 17, 113.
Tsujimoto, S., 2008. The prefrontal cortex: functional neural development during
early childhood. Neuroscientist 14, 345358.
Vanderschuren, L.J., Niesink, R.J., Van Ree, J.M., 1997. The neurobiology of social play
behavior in rats. Neurosci. Biobehav. Rev. 21, 309326.
Vasquez, R.A., 1997. Vigilance and social foraging in Octodon degus (Rodentia:
Octodontidae) in central Chile. Rev. Chil. Hist. Nat. 70, 557563.
Watt, D.F., Panksepp, J., 2009. Depression: an evolutionarily conserved mechanism
to terminate separation-distress? Areviewof aminergic, peptidergic, andneural
network perspectives. Neuropsychoanalysis 11, 751.
Weir, B.J., 1970. Themanagement andbreedingof somemorehystricomorphrodents.
Lab. Anim. 4, 8397.
White, P., Fischer, R., Meunier, G., 1982. The lack of recognition of lactating females
by infant Octodon degus. Physiol. Behav. 28, 623625.
Wiener, S.G., Bayart, F., Faull, K.F., Levine, S., 1990. Behavioral and physiological
responses to maternal separation in squirrel monkeys (Saimiri sciureus). Behav.
Neurosci. 104, 108115.
Wilson, S.C., 1982. Contact-promoting behavior, social development, and relation-
ship with parents in sibling juvenile degus (Octodon degus). Dev. Psychobiol. 15,
257268.
Wilson, S.C., Kleiman, D.G., 1974. Eliciting play: a comparative study. Am. Zool. 14,
341370.
Witvliet, M., van Lier, P.A., Cuijpers, P., Koot, H.M., 2009. Testing links between child-
hood positive peer relations and externalizing outcomes through a randomized
controlled intervention study. J. Consult. Clin. Psychol. 77, 905915.
Zahn-Waxler, C., Shirtcliff, E.A., Marceau, K., 2008. Disorders of childhood and ado-
lescence: gender and psychopathology. Annu. Rev. Clin. Psychol. 4, 275303.
Zehle, S., Bock, J., Jezierski, G., Gruss, M., Braun, K., 2007. Methylphenidate treatment
recovers stress-induced elevated dendritic spine densities in the rodent dorsal
anterior cingulate cortex. Dev. Neurobiol. 67, 18911900.
Ziabreva, I., Schnabel, R., Braun, K., 2000. Parental deprivation induces N-methyl
d-aspartate-receptor upregulation in limbic brain areas of Octodon degus: pro-
tective role of the maternal call. Neural Plast. 7, 233244.
Ziabreva, I., Schnabel, R., Poeggel, G., Braun, K., 2003. Mothers voice buffers
separation-induced receptor changes in the prefrontal cortex of Octodon degus.
Neuroscience 119, 433441.