# Investigating the ventral pallidum-ventral tegmental area circuit in cocaine relapse

> **NIH NIH F32** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $67,174

## Abstract

Project Summary/Abstract:
Rises in cocaine misuse and cocaine overdose deaths over the last decade illustrate the lack of therapeutic
interventions for individuals with cocaine use disorder (CUD). With abstinence as the only treatment for cocaine
cravings, a majority of individuals with CUD are vulnerable to relapse. The development of novel CUD
therapeutics relies on a thorough understanding of the neural mechanisms that drive cocaine craving and
relapse. Cocaine causes molecular adaptations within distinct neuronal subpopulations that leads to circuit-
specific changes in neural activity. A critical node of the reward circuit is the ventral pallidum (VP), as it receives
input from and projects to several regions that mediate cocaine-seeking behaviors. Activity from VP afferents to
the ventral tegmental area (VTA-projecting VP neurons) is required for cocaine relapse; however, the cellular
and molecular adaptations that occur within VTA-projecting VP neurons to promote cocaine-seeking, are
unknown. To better understand the pathology of CUD, this proposal will investigate how changes in
neuronal activity and gene expression within VTA-projecting VP neurons occur within cue-induced
reinstatement to cocaine-seeking. Using cocaine intravenous self-administration (IVSA) and chemogenetics
in mice, my preliminary data replicates a previous finding in rats that VTA-projecting VP neurons are required for
reinstatement of cocaine-seeking. In this proposal, I will employ IVSA, cutting-edge in vivo biosensors,
chemogenetics and molecular techniques to investigate the circuit-specific changes in VP neuronal activity and
gene expression that occur during reinstatement to cocaine-seeking. I hypothesize that cocaine engages VTA-
projecting VP neurons, leading to cocaine cue-induced 1) enhancement of VTA-projecting VP neuronal activity
and 2) increases in synaptic gene expression that accompany drug-seeking and relapse. In Specific Aim 1, I will
use fiber photometry to assess how cocaine-associated cues affected patterned calcium activity within VTA-
projecting VP neurons during cue-induced reinstatement. I will also examine how chemogenetic inhibition of
VTA-projecting VP neurons impacts changes in VTA-projecting VP calcium activity following the presentation of
cocaine-associated cues. In Specific Aim 2, I will perform ribosomal immunoprecipitation with RNA-Sequencing
to determine whether increases in synaptic gene expression within VTA-projecting VP neurons occurs following
reinstatement to cocaine-seeking. Further, I will examine whether inhibiting VTA-projecting VP neuronal activity
prevents reinstatement-induced changes in gene expression using chemogenetics and RNAScope. Together,
these experiments will identify novel mechanisms within VTA-projecting VP neurons neurons that mediate
reinstatement to cocaine-seeking. This proposal will also provide me with strong training in new research areas
that will support my independent career path in science.

## Key facts

- **NIH application ID:** 10463077
- **Project number:** 1F32DA056191-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Rianne Campbell
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-03-08 → 2025-03-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463077

## Citation

> US National Institutes of Health, RePORTER application 10463077, Investigating the ventral pallidum-ventral tegmental area circuit in cocaine relapse (1F32DA056191-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10463077. Licensed CC0.

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