Autism is a common, impairing neurodevelopmental disorder involving deficits in social interaction and social communication. Oxytocin (OT) is a nine amino acid peptide produced in the hypothalamus and stored in the posterior pituitary. 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 a proliferation of recent research examining the effects of intranasal OT on human behavior, including suggestions for its use as a therapeutic for various psychopathologies involving social deficits, including ASD. Phase 2 trials for use of intranasal OT in autism 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. Alarmingly, our preliminary data in animal models show that while administration of intranasal OT has positive effects of social behavior in the short-term, long-term effects at some dosages are negative. Aside from our pilot study, there have been no long-term studies of chronic intranasal OT use in humans or in ANY animal model;that is what we propose to do in this study.
The aim of the current study is to examine the developmental effects of chronic intranasal OT administered to two animal models of selective social behavior (prairie voles and titi monkeys), as well as one mouse model of the social deficits of autism. In the rodent models, dosage, frequency, and age of administration will be varied. The immediate social effects of administration, as well as long-term effects on social behavior, repetitive behavior, and anxiety will be explored, as well as changes to the OT and vasopressin systems and functional neural changes in response to social stimuli. In titi monkeys, we will administer the dosage being used in clinical trials and examine the short-term and long-term effects on social behavior, repetitive behavior, and anxiety. Finally, we will examine changes to local cerebral glucose metabolism in titi monkeys treated with chronic intranasal OT or vehicle via PET imaging, with a focus on areas that produce or have receptors for OT.

Public Health Relevance

Autism is a common, impairing neurodevelopmental disorder affecting 1 in 110 individuals. This proposal will investigate the long-term effects of chronic intranasal oxytocin, which has been proposed as a treatment for autism, in animal models.

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-BBBP-T (04))
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Kau, Alice S
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University of California Davis
Veterinary Sciences
Other Domestic Higher Education
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