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)
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Special Emphasis Panel (ZRG1)
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Kau, Alice S
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University of California Davis
Veterinary Sciences
Primate Centers
United States
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Bales, Karen L; Saltzman, Wendy (2016) Fathering in rodents: Neurobiological substrates and consequences for offspring. Horm Behav 77:249-59
Seelke, A M H; Yuan, S-M; Perkeybile, A M et al. (2016) Early experiences can alter the size of cortical fields in prairie voles (Microtus ochrogaster). Environ Epigenet 2:
Díaz-Muñoz, Samuel L; Bales, Karen L (2016) ""Monogamy"" in Primates: Variability, Trends, and Synthesis: Introduction to special issue on Primate Monogamy. Am J Primatol 78:283-7
Mendoza, Adrian; Ng, Jillian; Bales, Karen L et al. (2015) Population genetics of the California National Primate Research Center's (CNPRC) captive Callicebus cupreus colony. Primates 56:37-44
Bales, K L; Solomon, M; Jacob, S et al. (2014) Long-term exposure to intranasal oxytocin in a mouse autism model. Transl Psychiatry 4:e480
Ren, Dongren; Chin, Kelvin R; French, Jeffrey A (2014) Molecular variation in AVP and AVPR1a in New World monkeys (Primates, Platyrrhini): evolution and implications for social monogamy. PLoS One 9:e111638
Bales, Karen L; Perkeybile, Allison M; Conley, Olivia G et al. (2013) Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles. Biol Psychiatry 74:180-8