# Defining the role of the estrous cycle in cocaine addiction vulnerability

> **NIH NIH F32** · VANDERBILT UNIVERSITY · 2021 · $10,601

## Abstract

Project Summary/Abstract
Cocaine use disorder is a public health concern with no effective pharmacotherapies, despite clear need. Even
though both males and females become addicted to cocaine, females transition to addiction faster, have more
trouble quitting cocaine and relapse more frequently than men. Many of these features have been captured in
preclinical models of addiction where female nonhuman primates and rodents take more drug, work harder to
obtain drug and are more sensitive to cue- and stress-primed reinstatement. Studies have shown that the
increased cocaine-taking and drug craving fluctuates with the menstrual cycle (estrous cycle in rodents) where
consumption and craving are most evident during estrus (when ovarian hormone levels are high). Other evidence
shows that the ventral tegmental area (VTA) to nucleus accumbens (NAc) dopamine (DA) neurons are more
active at baseline and release more DA in response to phasic stimulation during this same period. While there
have been numerous studies focusing on defining the causal link between specific hormones and alterations in
dopamine system function, understanding how the intact estrous cycle drives differences in cocaine
reinforcement is critical to understanding sex differences in vulnerability. Here we aim to understand how the
VTA to NAc DA system is altered in intact cycling females over the estrous cycle to change reinforcement for
cocaine. In this proposal, we will use a combination of cutting-edge techniques such as pathway-specific
optogenetic stimulation and designer receptors exclusively activated by designer drugs approaches in vivo to
isolate the VTA to NAc DA neurons and understand the effect of the estrous cycle on the function of these DA
neurons and the effect this has on cocaine-taking behavior. We will then use ex-vivo slice voltammetry to
precisely understand the mechanisms involved in the increased DA functioning during estrus. We will determine
if the effect is happening at the level of local circuits within the NAc, DA synthesis, or changes in the readily
releasable pool of DA. These experiments will elucidate the effect of the estrous cycle on the VTA to NAc DA
pathway and will provide new information about biological factors that increase vulnerability to drug addiction.
This will provide new targets for pharmacotherapy development as we learn more about how to modulate the
DA system in ways that will decrease cocaine-taking behavior without producing addictive or aversive effects.

## Key facts

- **NIH application ID:** 10148747
- **Project number:** 5F32DA047777-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Amy R Johnson
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $10,601
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148747

## Citation

> US National Institutes of Health, RePORTER application 10148747, Defining the role of the estrous cycle in cocaine addiction vulnerability (5F32DA047777-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10148747. Licensed CC0.

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