# Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $697,498

## Abstract

There is an estimated 5.7 million Americans that are current cocaine users and, at present, there are no FDA-
approved treatments for cocaine use disorders. This research project is a continuation of funded work aimed at
understanding the behavioral, pharmacological and neurobiological variables influencing the reinforcing effects
of cocaine in a unique nonhuman primate model: intravenous cocaine self-administration (SA) in socially
housed cynomolgus monkeys. The goals of the present application are to continue using this homologous
animal model to examine the mechanisms of action mediating the interactions between social hierarchy and
environmental and pharmacological modulation of cocaine self-administration in female and male monkeys.
Using PET imaging, over the previous funding period, we have noted sex- and social-rank related differences
in dopamine (DA) D2/D3 receptor (D2/D3R) and kappa opioid receptor (KOR) availability in cocaine-naïve
monkeys through long-term cocaine SA. Consistent with these sex- and social-rank differences, we noted
individual differences in response to several pharmacological manipulations. In Aim 1, we propose to extend
the characterization of sex- and social-rank differences in cocaine SA to examine several behavioral
interventions. For these studies, monkeys will choose between cocaine and food and the following
interventions will be examined: delay discounting involving both food and cocaine delays; changes in the
magnitude of the food reinforcer, to better model contingency management; and punishment, using a KOR
agonist (positive punishment), which will be important since we have measures of KOR availability in these
monkeys, as well as using response-contingent timeouts (negative punishment). The studies in Aim 2 will
examine the effects of chronic drug treatments in socially housed monkeys self-administering cocaine in the
context of an alternative, non-drug, reinforcer (food-cocaine choice). We will also combine chronic
pharmacological treatments with behavioral interventions in an effort to further decrease cocaine choice.
Importantly, cognitive performance will be assessed to better determine if the intervention has unwanted side
effects. The goals of Aim 3 are to examine how cocaine SA and chronic drug treatment differentially affects
D2/D3R and KOR availability, using a within-subjects design, in socially housed female and male monkeys.
The scientific premise is that different mechanisms maintain cocaine SA based on social rank and sex and
thus different intervention strategies (both behavioral and pharmacological) will be required to produce a
positive outcome in these groups. We are proposing a preclinical personalized-medicine strategy for treating
cocaine abuse that incorporates sex and social variables.

## Key facts

- **NIH application ID:** 10904111
- **Project number:** 2R01DA017763-16A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Michael A Nader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $697,498
- **Award type:** 2
- **Project period:** 2001-09-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904111

## Citation

> US National Institutes of Health, RePORTER application 10904111, Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys (2R01DA017763-16A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904111. Licensed CC0.

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