# Kappa Opioid Receptor Availability, Social Rank, and Cocaine Self-Administration in Female and Male Monkeys

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $46,752

## Abstract

Cocaine use disorder (CUD) persists as a worldwide public health problem for which there is no FDA-approved
pharmacotherapy. Of clinical significance, in the US, cocaine use is increasing, alongside cocaine overdose
deaths, which have more than tripled from 2012 to 2018 [1, 2]. A gap in the literature and the primary focus of
this application, is to extend research from the dopamine system, associated with euphoria, to the
dynorphin/kappa opioid receptor (KOR) system, implicated in the “dark side” of addiction. This research project
utilizes a highly homologous nonhuman primate model, incorporating social behavior with intravenous drug self-
administration (SA) and positron emission tomography (PET), in drug-naive female and male monkeys. The
proposed longitudinal, within-subject study design will further our understanding of the neurobiology associated
with the vulnerability and maintenance of cocaine abuse. The initial Aim 1 of this proposal used PET imaging
with a KOR radiotracer, [11C]EKAP, to obtain baseline measures of KOR availability and assess the relationship
between KOR availability and social rank in cocaine-naïve male and female monkeys. The studies in that Aim
have been completed. Overall, the lowest receptor availability across all regions of interest were observed in
dominant females and subordinate males; based on previous studies, the two most vulnerable phenotypes to
cocaine reinforcement. The baseline assessment of KOR measures allows the ability to assess the relationship
between receptor availability and vulnerability of cocaine abuse (Aim 1), as well as how those measures change
following chronic cocaine self-administration (Aim 2). In addition, the studies in Aim 3 will assess clinically
relevant factors associated with withdrawal/abstinence and assess the neural plasticity of KOR system following
protracted abstinence. The use of PET as a biomarker related to vulnerability and treatment outcome may
provide evidence for a personalized medicine approach to treating CUD.

## Key facts

- **NIH application ID:** 10389440
- **Project number:** 1F31DA053776-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Bernard N Johnson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389440

## Citation

> US National Institutes of Health, RePORTER application 10389440, Kappa Opioid Receptor Availability, Social Rank, and Cocaine Self-Administration in Female and Male Monkeys (1F31DA053776-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389440. Licensed CC0.

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