Neurologic Weekly. 2014 Feb 21.

Sexual Motivation in Rats with Fragile X Syndrome: Neurological Alignment with Autism
Keyes A , Smith J , et al. Keywords: Autism, Fragile X Syndrome, Sex, Sexual Motivation, fMRI Abstract: This study will look at the neurological reaction of a rat with Fragile X Syndrome, which usually leads to a degree of Autism. By using an MRI, it will specifically look at the male rat brains reaction when it is introduced to the scent of a fertile female rat. None of the male rats that were studied had been exposed to the scent of a female rat prior to this experiment. Initial scans of the rat brain activity without any stimuli will be taken to use as control data. A researcher will bring a female rat into the MRI room while another researcher is taking magnetic scans of the nave male rat brain. The control results of the scans prior to female presence in the room will then be compared to the MRI scans taken when a female was introduced into the males environment to see if there is any significant difference. We will also compare the scans of the Fragile X rat brain to a normal male rats brain when they initially smell the scent of a sexually receptive female rat. These two comparisons will help us determine which areas of the brain of a Fragile X male rat reacted to the female scent, as well as if those areas are similar to a normal neurological rat brain stimulation that is under the same circumstances. We found that the typical brain areas associated with sexual arousal and motivation were not strongly stimulated in the male rats with Fragile X Syndrome when they were exposed to the fertile female rat smell. The areas that we focused on when comparing the data were the amygdala, nucleus accumbens, ventral tegmental area (VTA), and the pituitary gland. Introduction: In regards to autism spectrum disorders, scientists are constantly discovering new findings related to its etiology, prevalence, symptoms and proper treatment. There have been many more studies trying to determine its genetic link, and also some that suggest that the environmental component is much stronger than previously thought (Tchaconas et al. 2013). With that in mind, scientists do categorize certain types of autism depending on their etiology or characteristics. A common type is Fragile X Syndrome and Autism, also known as FXS + Aus. FXS alone is the most common inherited cause of intellectual disability. The disease occurs when one of the X chromosomes legs is either broken or significantly shorter than the other. Fragile X Syndrome has a behavioral phenotype that consists of many characteristically autistic features such as poor eye contact, perseverative behavior, motor issues, self-injurious behaviors,

social avoidance, and delayed or odd speech (Wolff et al. 2012). These social behavior issues lead to differences in how FXS Autistic people deal with fear, reward and sexual motivation. All three characteristics are basic and necessary in regards to evolution. The research on people with FXS+ Aus and how they react to fear and reward has been increasing in popularity in the past years. Yet, the research on sexual motivation in people with FXS Autism is scarce. There has been some research on how high functioning Autistic people function sexually. Byers et al. (2013) looked at how individuals with Autism Spectrum Disorders (ASD) function sexually in regards to sexual knowledge, sexual behavior engaged in alone, sexual affect, sexual behavior with a partner, sexual cognitions, and sexual response. They found that participants were not strongly motivated to find a partner given their moderate desire for dyadic sexual activity, some sexual anxiety, and only moderate levels of sexual arousability (Byers et al. 2013). There is also minimal research looking into FXS Autism and sex using MRI techniques. Even general examination of certain brain structures and systems in humans with FXS is limited. Bruno et al. provided evidence that metabolite differences in the caudate nucleus is linked to the neural deficits in people with FXS (2013). They determined this using a 3 Telsa MRI Scanner with single channel quadrature head coils and single-voxel MRS, focused on the caudate brain region. Our research imaging brains of male rats with the FXS mutation and their responses to sexual arousal will add significant information to an area of FXS+ Aus that is lacking. There is little if any information on sexual motivation and sexual behavior in ASD or FX. To this end, we used functional magnetic resonance imaging (fMRI) to study changes in brain activity in a transgenic FX rats in response to the odors of sexual receptive female rats. We hypothesize that Fragile X animals would demonstrate a normal reaction to sexually arousing stimuli. Interestingly, FX animals showed a heightened response to the sexual odors both in behavioral tests and during imaging. Unexpected was a decreased or suppressed display of behavior and brain activity in normal wild-type controls. These findings are discussed in the context of understanding the effects of a single gene mutation on a complex evolutionarily conserved behavior. Subjects: We tested 11 Sprague Dawley male rats. All of the transgenic Fragile X Sprague Dawley rats that were bought from Sage and used in this study were individually housed and maintained on a 12:12 hour, light:dark cycle. The rats were provided food and water. The food was the same rat chow that the Sage Company fed them as they were being bred. The animals were obtained and cared for in accord with the Guide for the Care and Use of Laboratory Animals and follow the guidelines that are laid out in the American Association for Laboratory Animal Science and the National Institutes of Health. These rats have never been exposed to any smells that would activate their sexual motivation.

Works Cited: Bruno JL, Shelly EW, Quintin EM, Rostami M, Patnaik S, Spielman D, Mayer D, Gu M, Lightbody AA, Reiss AL. Aberrant basal ganglia metabolism in fragile X syndrome: a magnetic resonance spectroscopy study. J Neurodev Disord. 2013 Aug 28;5(1):20. doi: 10.1186/1866-1955-5-20. PubMed PMID: 23981510; PubMed Central PMCID: PMC3766683. http://www.ncbi.nlm.nih.gov/pubmed/23981510 Byers, E. S., Nicols, S., & Voyer, S. D. (2013). Challenging stereotypes: sexual functioning of single adults with high functioning autism spectrum disorder. Journal of Autism and Developmental Disorders, 43(11), 2617-2627. http://link.springer.com.ezproxy.neu.edu/article/10.1007/s10803-0131813-z Wolff, J.J., Bodfish, J.W., Hazlett, H.C., Lightbody, A.A., Reiss, A.L., Piven, J. (2012). Evidence of a distinct behavioral phenotype in young boys with fragile X syndrome and autism. Journal of the American Academy of Child & Adolescent Psychiatry, 2012-12-01, Volume 51, Issue 12, Pages 1324-1332. http://www.sciencedirect.com.ezproxy.neu.edu/science/article/pii/S08908 56712006879 Response Letter I want to thank the people who reviewed my paper. Because of my omission of the context note, it was hard for them to fully review my paper, but what they did advise on was helpful. The idea of adding an abstract to give the audience a better understanding of what the research is was a great idea that I used. I also made some edits to the introduction section to make it flow a bit better and be clearer. Lastly, I added a title and publication line to the beginning to make it look more like a legitimate research paper.