# Antecedents and Consequences of Cocaine Taking: Impact of Oxytocin

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $579,018

## Abstract

Dominance behaviors and social status in primates affects physiology, neural structure, behavior and response
to drugs of abuse. Oxytocin (OXT), a peptide hormone associated with dominance behavior modulates cocaine
self-administration and is associated with hippocampal (HC) volume. Male dominance commonly relies on
aggression while female dominance commonly relies on grooming. We hypothesize that the different behaviors
associated with male and female social structure account for the sex differences in cocaine self-administration
observed in socially-housed cynomolgus monkeys. Thus, both dominance behavior and sex moderate drug
response, yet studies on the interaction of these two variables are sorely missing. We hypothesize that
dominance behavior is a significant factor accounting for biologically relevant variability in research with non-
human primates. Therefore, we propose a prospective study on the effects of sex, menstrual cycle, dominance
behavior and cocaine self-administration on OXT levels and HC volume in rhesus monkeys and the effects of
manipulating OXT on cocaine self-administration. We will use standardized, same-sex dyad-interaction tests to
obtain a dominance-index for each monkey. Our preliminary data show that the dominance-index, even in
singly-housed non-human primates, is related to striatal dopamine release, the reinforcing effects of cocaine,
the appetitive effects of amphetamine, and HC volume. Thus the dominance-index is a relevant measure of a
behavioral trait related to both social and non-social reinforcers. Aim 1. Determine the effect of dominance-
index on HC volume and OXT levels in male (n = 10) and female (n = 10) rhesus monkeys. Aim 2a. Determine
the reinforcing effects of self-administered i.v. cocaine and palatable food as a function of dominance-index.
Aim 2b. Determine the effects of menstrual cycle and dominance-index on the reinforcing effects of self-
administered i.v. cocaine and palatable food. Aim 3. Determine the effects of (9 mo) cocaine self-
administration on HC volume and OXT levels as a function of the dominance-index. Aim 4. Determine the
effects of a) increasing OXT levels by acute administration of SOC1, developed by Iain MacGregor, b)
decreasing OXT effects by acute administration of the OXT antagonist 2,5- diketopiperazine (DTP) and c)
SOC1 + DTP on cocaine self-administration as a function of the dominance-index.
Impact. We will dynamically and prospectively track HC volume and OXT levels in male and female rhesus
monkeys in order to assess the extent to which these measures are risk factors for drug use, consequences of
drug use, or both. By using naturally varying dominance-indexes, we will be able to tease out the effects of
environmental conditions from cocaine taking. This proposal will provide an empirical basis for the
development of biologically-informed manipulations of the oxytocin system, and behaviorally-informed
treatments based on social behavior for both males and females.

## Key facts

- **NIH application ID:** 9747260
- **Project number:** 5R01DA041543-03
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Suzette M Evans
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $579,018
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9747260

## Citation

> US National Institutes of Health, RePORTER application 9747260, Antecedents and Consequences of Cocaine Taking: Impact of Oxytocin (5R01DA041543-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9747260. Licensed CC0.

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