While intensive behavioral intervention delivered early in life improves social functioning for some children with autism spectrum disorder (ASD), current pharmacological treatments are limited to targeting only peripheral symptoms such as aggression, anxiety, and depression. Novel pharmacological interventions specifically targeting social behavior delivered in parallel with behavioral intervention holds the promise of improving quality of life for many individuals with ASD. Development of pro-social pharmacological treatments will depend upon the successful translation of basic neuroscience research into safe and effective medicines and will require the use of sophisticated animal models. While current ASD drug discovery efforts have relied primarily upon mouse models to evaluate compound efficacy, pharmacological interventions targeting the complex social and communication deficits of ASD may ultimately require the use of an animal model more closely related to humans. Rhesus monkeys are considered the biomedical model species of choice due to their resemblance in human physiology, neuroanatomy and behavior. Although there are currently no validated nonhuman primate models of ASD, we believe that natural variation in sociability of rhesus monkeys provides a novel model to evaluate the efficacy of pro-social pharmacological treatments. We have established behavioral phenotyping protocols to identify low-social and high-social juvenile monkeys in their natal field cages and to reliably quantify changes in social functioning in a laboratory setting. Our battery of behavioral assays can be used to directly compare social outcome measures with both mouse models (i.e., high-throughput assays of sociability) and clinical populations (i.e., non-invasive eye tracking). With these developments, the nonhuman primate model is poised to provide a valuable test bed for evaluating innovative treatments targeting the core social deficits of ASD. We propose to first utilize this model to evaluate one of the most promising avenues of ASD treatment research - the oxytocin system. Although nasal oxytocin therapy is being promoted as a safe and promising therapy for ASD, we know very little about the efficacy or mechanism of oxytocin treatment in humans. Here we propose to utilize a well-characterized population of juvenile macaque monkeys to systematically evaluate the effects of intranasal oxytocin administration on primate sociability. We anticipate that the methods developed in the proposed research will result in a standard nonhuman primate testing platform that can be used to evaluate numerous future pharmacological interventions targeting the social deficits of ASD.
We anticipate that novel pharmacological interventions targeting core features of autism will be forthcoming in the near future and will ultimately requir sophisticated animal models to evaluate treatment efficacy. The proposed nonhuman primate model provides critical bridge between mouse models and clinical populations.
| Bauman, M D; Schumann, C M (2018) Advances in nonhuman primate models of autism: Integrating neuroscience and behavior. Exp Neurol 299:252-265 |
| Careaga, Milo; Murai, Takeshi; Bauman, Melissa D (2017) Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry 81:391-401 |
| Platt, Michael L; Seyfarth, Robert M; Cheney, Dorothy L (2016) Adaptations for social cognition in the primate brain. Philos Trans R Soc Lond B Biol Sci 371:20150096 |
