Autism is a common, impairing neurodevelopmental disorder affecting 1 in 88 individuals. Oxytocin (OT), is a hormone produced in the brain and stored in the posterior pituitary for release into the periphery. OT regulates the formation of close selective social bonds and has been implicated in the social dysfunction found in autism spectrum disorders (ASD). There has been an enormous increase in recent research examining the effects of intranasal OT on human behavior, including suggestions for its use as a therapeutic for various psychopathologies including ASD. Phase 2 trials for use of intranasal OT in ASD are underway for children 12-18 years of age ( identifier: NCT01256060), and OT is already frequently prescribed in the United States to children with ASD. OT is also in clinical trials for a number of other disorders, including schizophrenia and social anxiety - thus concerns about its usage are not limited to its use for ASD. Alarmingly, our recent research using animal models suggests that chronic administration of OT at some dosages can have long-term, adverse effects on social bonding. In addition to its effects on social behavior, OT is also crucial to the regulation of reproduction, and is involved in reproductive behavior, sperm production and transport, orgasm, birth, and lactation. This proposal is a competitive revision to an already funded study examining the effects of chronic exposure to intranasal OT. The funded study will produce an extremely valuable set of monkeys treated chronically with either intranasal OT or intranasal saline, a cohort which is unlikely ever to be re-created, and to which it would be advantageous to add additional outcome measures.
The aims of the original grant are to examine the effects of chronic intranasal OT on social behavior and socially related neural function. With this revision, we are seeking additional funding to characterize the long-term reproductive effects of these treatments. We will examine the role of chronic exposure to intranasal OT on reproductive maturation, reproductive behavior and fertility, reproductive potential, and lactation. Our hypothesis is that chronic intranasal OT treatment may lead to changes in reproductive maturation, function and behavior, and, particularly in males, changes in sperm transport due to alteration in OT receptors in the male reproductive tract.
These aims are not covered in the original R01 application. This revision, as with the original grant, is carried out in close collaboration with one of the scientists carrying out a clinical intranasal OT trial in humans;in addition, we have added experts in reproductive biology.

Public Health Relevance

Autism is a common, impairing neurodevelopmental disorder affecting 1 in 88 individuals. Oxytocin is a hormone produced in the brain which is known to be involved in both social behavior and reproduction, and which is already being used to treat autism in humans. This proposal would examine reproduction in a group of monkeys which are already receiving intranasal oxytocin as part of a different, already funded study.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kau, Alice S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Davis
Veterinary Sciences
Primate Centers
United States
Zip Code
Freeman, Sara M; Rebout, Nancy; Bales, Karen L (2018) Effect of reward type on object discrimination learning in socially monogamous coppery titi monkeys (Callicebus cupreus). Am J Primatol 80:e22868
Seelke, Adele M; Rhine, Maya A; Khun, Konterri et al. (2018) Intranasal oxytocin reduces weight gain in diet-induced obese prairie voles. Physiol Behav 196:67-77
Kanthaswamy, Sree; Bales, Karen L (2018) Evaluating the genetic status of a closed colony of titi monkeys (Callicebus cupreus) using multigenerational pedigrees. J Med Primatol 47:139-141
Guoynes, C D; Simmons, T C; Downing, G M et al. (2018) Chronic Intranasal Oxytocin has Dose-dependent Effects on Central Oxytocin and Vasopressin Systems in Prairie Voles (Microtus ochrogaster). Neuroscience 369:292-302
Freeman, Sara M; Ngo, Julie; Singh, Bhavdeep et al. (2018) Effects of Chronic Oxytocin Administration and Diet Composition on Oxytocin and Vasopressin 1a Receptor Binding in the Rat Brain. Neuroscience 392:241-251
Larke, Rebecca H; Toubiana, Alice; Lindsay, Katrina A et al. (2017) Infant titi monkey behavior in the open field test and the effect of early adversity. Am J Primatol 79:
Perkeybile, Allison M; Bales, Karen L (2017) Intergenerational transmission of sociality: the role of parents in shaping social behavior in monogamous and non-monogamous species. J Exp Biol 220:114-123
Duchemin, Auriane; Seelke, Adele M H; Simmons, Trenton C et al. (2017) Localization of oxytocin receptors in the prairie vole (Microtus ochrogaster) neocortex. Neuroscience 348:201-211
Bales, Karen L (2017) Parenting in Animals. Curr Opin Psychol 15:93-98
Bales, Karen L; Saltzman, Wendy (2016) Fathering in rodents: Neurobiological substrates and consequences for offspring. Horm Behav 77:249-59

Showing the most recent 10 out of 17 publications