# Sex differences in operant cocaine memories

> **NIH NIH P20** · UNIVERSITY OF MISSISSIPPI MED CTR · 2024 · $210,999

## Abstract

The inability to maintain abstinence is a trademark of addiction yet effective maintenance therapies 
remain elusive. Women may face unique issues with substance abuse treatment, as research indicates 
that psychological and biological responses to drugs of abuse differ in women compared to men. Women 
tend to show greater drug dependence, progress more quickly from casual drug use to dependence, have 
greater difficulty quitting, and have shorter periods of abstinence than men. These effects have been 
similarly observed in female animal models. Thus, understanding circuit and molecular signatures that 
drive increased drug-seeking among females is critical to the development of effective SUDs therapies. 
We have developed a novel behavioral model termed the seeking-persistence paradigm (SPP) that was 
adapted from standard drug abstinence paradigms. The seeking-persistence paradigm is used to 
investigate the influence of intervention during initial abstinence on long-term drug-seeking behaviors. 
Indeed, cocaine-seeking during initial abstinence strongly correlates with seeking after drug-abstinence. 
These results reflect clinical studies indicating that craving during initial abstinence predicts relapse rates. 
We have previously identified that the dorsal hippocampus is a crucial target for sex-specific modulation of 
cocaine-seeking on ED1. Prior reports show projections from the dorsal hippocampus selectively 
modulate memory strengthening or facilitate extinction, dependent on whether they terminate in the 
prelimbic cortex, or infralimbic cortex, respectively. Our preliminary data suggest that sexually-divergent 
projections of the dHPC to prelimbic and infralimbic cortical areas may underlie sex differences in 
persistent cocaine seeking during extinction. Herein, we will test the hypothesis that 
hippocampal-prelimbic cortex neurocircuitry drives the behavioral expression of cocaine memory 
strengthening in female rats (Aim 1), and hippocampal infralimbic cortex neurocircuitry drives the 
behavioral expression of cocaine memory extinction in male rats (Aim 2). In each aim, we will combine 
chemogenetic (DREADDs), and functional genomic methods (viral tracing, RNA-sequencing, and 
single-cell RNA-sequencing), to ultimately provide key information on the impact of context-induced 
cocaine seeking behavior on relapse risk through the novel analysis of the contribution of memory 
systems (dHPC ->PL, dHPC-> IL) and sex differences therein.

## Key facts

- **NIH application ID:** 11087350
- **Project number:** 5P20GM144041-02
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Amy Kohtz
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,999
- **Award type:** 5
- **Project period:** 2024-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11087350

## Citation

> US National Institutes of Health, RePORTER application 11087350, Sex differences in operant cocaine memories (5P20GM144041-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11087350. Licensed CC0.

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