# Investigation of how sex steroids and nicotinic acetylcholine receptors promote cocaine self-administration

> **NIH NIH K00** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $80,913

## Abstract

PROJECT SUMMARY/ABSTRACT
About 12 million individuals over the age of 12 have a substance use disorder (SUD). Cocaine is involved 
in about 1 in 5 overdoses in the United States and is abused by both men and women. Women are more 
vulnerable to the rewarding effects of cocaine and more rapidly progress from initial use to dependence than 
men but the neurobiological mechanisms that contribute to these differences are yet to be determined. A 
limitation of the current work investigating sex differences in preclinical research is that the research is primarily 
focused on hormonal contributions that may be driving sex differences. There is little understanding of how sex 
steroids and other neurobiological mechanisms contribute to cocaine dependence. The overall goal of this 
project is to identify the effects of a history of cocaine self-administration on sex steroids and nicotinic 
acetylcholine receptor (nAChRs) subunit expression and to test the hypothesis that decreased nAChRs 
alpha 5 (ɑ5) in the dorsal hippocampus (dHIPP) produced by decreased progesterone levels promote 
cocaine self-administration behavior. Aim 1 will use single-cell transcriptomics to identify sex differences in 
the dysregulated transcriptional networks in rats with a history of compulsive-like cocaine self-administration 
using brain (dHIPP), adrenal, pituitary, reproductive organ samples. Aim 2 will causally investigate the role of 
the nAChR ɑ5 in the dHIPP and progesterone on cocaine self-administration behavior using an AAV-ShRNA to 
knock down nAChRs ɑ5 in the dHIPP and pharmacology to block the progesterone receptor. These projects will 
be the first to look at associations between sex steroids and nAChR ɑ5 in the dHIPP on cocaine selfadministration in both sexes. My Sponsor, Dr. Olivier George (UCSD) is an expert on the neurobiology of drugs 
of abuse and addiction and is recognized as an innovative leader in the field of drug abuse and, therefore, the 
perfect fit to mentor me for the proposed research. The proposed Research and Training Plans will deepen my 
knowledge of transcriptomics, the cholinergic system, the hippocampus, and neuroendocrinology in addictionlike phenotypes and will expand my expertise in cocaine dependency. The training I will receive in single-cell 
transcriptomics, ELISAs, bioinformatics, intrajugular catheter surgeries, and advanced operant paradigms will 
give me the skills necessary to answer questions focused on cell-specific differences in males and females that 
may be driving dysregulation of reward circuitry pre- and post-drug exposure. The training I have received in the 
F99 phase and the training I will receive in the K00 phase will allow me to establish a lab where I can research 
my long-term research goal of investigating the mechanisms underlying maladaptive addiction behaviors and 
how these behaviors differentiate by sex.

## Key facts

- **NIH application ID:** 10625154
- **Project number:** 8K00DA057923-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Elizabeth Sneddon
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $80,913
- **Award type:** 8
- **Project period:** 2020-12-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10625154

## Citation

> US National Institutes of Health, RePORTER application 10625154, Investigation of how sex steroids and nicotinic acetylcholine receptors promote cocaine self-administration (8K00DA057923-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10625154. Licensed CC0.

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