# The effect of ethanol self-administration on cocaine reinforcement in male and female monkeys

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $48,974

## Abstract

In the U.S., substance use disorders (SUDs) cost more than $820 billion dollars a year and continue to present
significant challenges to health and justice systems [1, 2]. Although there are clinically effective
pharmacotherapies for numerous drugs of misuse there are currently no FDA-approved treatments for cocaine
use disorder (CUD), despite decades of preclinical research. The lack of effective medications for CUD
suggests that there are gaps in translatability between preclinical and clinical research. One possible cause of
this gap is the fact that most individuals with CUD are using more than one drug at the same time [3]. One
substance that is commonly co-used with cocaine is alcohol and estimates suggest that up to 90% of
individuals who misuse cocaine also co-use alcohol [4, 5]. While the mechanistic basis of alcohol and cocaine
co-use is still poorly understood, research suggests that ethanol may enhance cocaine’s elevation of striatal
dopamine concentrations, thus increasing cocaine’s reinforcing effects [6]. It is also important to note that the
co-use of cocaine and alcohol is associated with more severe cocaine dependence, higher rates of psychiatric
co-morbidities, and poorer treatment outcomes [7-9]. Despite this, the vast majority of substance abuse
research has focused on the use of cocaine or alcohol in isolation, which may limit the clinical translatability of
research findings. Given this, the aims of this NRSA are to characterize the effects of ethanol on vulnerability to
cocaine reinforcement (Aim 1), to examine how ethanol influences maladaptive cocaine choice in the presence
of an alternative reinforcer (Aim 2), and to explore a potential pharmacotherapy for cocaine and alcohol co-use
(Aim 3) in a translational nonhuman primate model of substance use. I hypothesize that ethanol consumption
will enhance the potency of cocaine reinforcement, resulting in greater sensitivity in studies of acquisition and
the ability of alternative non-drug reinforcers to decrease cocaine choice. I also hypothesize that a combination
of modafinil analog JJC8-091 and naltrexone will reduce both cocaine and ethanol self-administration. These
findings will build on other data providing evidence as to why people co-use multiple drugs (e.g., enhance
reinforcement) and how the study of pharmacological interventions need to consider these conditions.

## Key facts

- **NIH application ID:** 10898434
- **Project number:** 1F31DA060614-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Mia Isabel Rough
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898434

## Citation

> US National Institutes of Health, RePORTER application 10898434, The effect of ethanol self-administration on cocaine reinforcement in male and female monkeys (1F31DA060614-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10898434. Licensed CC0.

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