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

> **NIH NIH R01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $736,213

## Abstract

Drug abuse continues to be a major public health problem worldwide, with over 1.5 million Americans
confirming current cocaine use and, at present, there are no FDA-approved treatments for cocaine addiction.
This research project is a continuation of funded work aimed at understanding the neurobiology of cocaine
abuse in a unique nonhuman primate model: intravenous cocaine self-administration 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 drug self-administration in female and male monkeys. Over
the previous funding period, we have noted sex- and social-rank related differences in vulnerability to cocaine
self-administration (SA) and in response to several acute pharmacological manipulations. In Aim 1, we will
extend this characterization to chronic drug treatment in socially housed monkeys self-administering cocaine in
the context of an alternative, non-drug, reinforcer (food-cocaine choice). We will also examine how these
treatments affect cocaine-induced reinstatement. The studies in Aim 2 will extend these sex- and social-rank
differences to impulsive-like behavior by implementing delays to food and cocaine. When food is delayed, we
hypothesize that females will be more “impulsive” compared to males and when cocaine is delayed,
subordinates will require longer delays to shift preference. The effects of long-term cocaine SA and chronic
drug treatment on cognitive performance in socially housed monkeys will be examined in Aim 3. We
hypothesize that cognitive performance of females will be more disrupted by cocaine than performance by
males and that subordinate monkeys will be more sensitive than dominant animals. Recently, we reported
social-rank related differences in brain glucose utilization using [18F]fluorodeoxyglucose and PET and in
dopamine D2/D3 receptor availability using [11C]raclopride. The goal of Aim 4 is to examine how cocaine SA
and chronic drug treatment differentially affects glucose utilization and D2/D3 receptor availability 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 drugs will be required to produce a positive outcome in these
groups. We are proposing a preclinical personalized-medicine strategy for treating drug abuse that
incorporates sex and social variables. Results from these studies should aid in the development of novel and
individualized treatment strategies for drug addiction.

## Key facts

- **NIH application ID:** 10225465
- **Project number:** 5R01DA017763-14
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Michael A Nader
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $736,213
- **Award type:** 5
- **Project period:** 2004-05-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225465

## Citation

> US National Institutes of Health, RePORTER application 10225465, Mechanisms Mediating Cocaine Abuse in Socially Housed Female and Male Monkeys (5R01DA017763-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10225465. Licensed CC0.

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