The brain neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important roles in altering neural circuits that regulate social behavior. These ligands regulate normative social function in a host of areas, including social attachment, parental behavior, aggression, and complex social cognition. In pathological brain/behavior conditions, many disorders are characterized by dramatic deficits in the social realm. Knowledge of the way OT and AVP alter cellular function in neurons has the potential to both identify mechanisms that produce social dysfunction and to design compounds that normalize cellular function and behavior. The present project takes advantage of the discovery of novel OT ligand structure, and variation in cellular receptors for OT and AVP in the marmoset, a species that exhibits social monogamy, infant care by males, and a family-like social structure.
The first aim will characterize the effects of ligand diversity on the alteration of behavior in a variety of social domains by using in vivo behavioral pharmacology. These domains include male-female attachment, infant care, mate-defense aggression, and social cooperation/altruism.
The second aim will quantify the receptor pharmacology and binding characteristics of the ligand variants with the cell membrane G protein-coupled receptors for these related ligands.
The final aim will define the specific modifications in G protein-mediated cell signaling processes brought about by these ligands to determine if ligand variation that modifies social behavior does so through specific or `biased' activation of different signaling pathways. Collectively, these three aims will provide important insights into the ways in which neurons and behavior are modified by OT and AVP ligand variants, leading to enhanced knowledge of the neurobiology of social behavior. The project can point to potential options for designing neuropeptide ligand- receptor complexes that could serve as effective tools to treat social dysfunction.

Public Health Relevance

Normal social function is critical to everyday life and dysfunction in the social realm occurs commonly in psychopathology and behavioral disorders. This project will examine how modifications in critical brain neuropeptide signaling molecules, oxytocin and vasopressin, alter cellular processes and modify social behavior. The results have important implications for potential treatments and drug designs that selectively treat dysfunction in social behavior.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD089147-05
Application #
9948492
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Bremer, Andrew
Project Start
2016-08-20
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Nebraska Omaha
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
190827162
City
Omaha
State
NE
Country
United States
Zip Code
68182
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Cavanaugh, Jon; Mustoe, Aaryn; French, Jeffrey A (2018) Oxytocin regulates reunion affiliation with a pairmate following social separation in marmosets. Am J Primatol 80:e22750
Cavanaugh, Jon; Mustoe, Aaryn; Womack, Stephanie L et al. (2018) Oxytocin modulates mate-guarding behavior in marmoset monkeys. Horm Behav 106:150-161
Mustoe, Aaryn; Taylor, Jack H; French, Jeffrey A (2018) Oxytocin structure and function in New World monkeys: from pharmacology to behavior. Integr Zool 13:634-654
Taylor, Jack H; Intorre, Allison A; French, Jeffrey A (2017) Vasopressin and Oxytocin Reduce Food Sharing Behavior in Male, but Not Female Marmosets in Family Groups. Front Endocrinol (Lausanne) 8:181
Taylor, Jack H; Cavanaugh, Jon; French, Jeffrey A (2017) Neonatal oxytocin and vasopressin manipulation alter social behavior during the juvenile period in Mongolian gerbils. Dev Psychobiol 59:653-657
French, Jeffrey A (2016) Genes, dopamine pathways, and sociality in primates. Proc Natl Acad Sci U S A 113:6325-7
French, Jeffrey A; Taylor, Jack H; Mustoe, Aaryn C et al. (2016) Neuropeptide diversity and the regulation of social behavior in New World primates. Front Neuroendocrinol 42:18-39
Cavanaugh, Jon; Huffman, Michelle C; Harnisch, April M et al. (2015) Marmosets treated with oxytocin are more socially attractive to their long-term mate. Front Behav Neurosci 9:251