# Mechanisms of Nucleus Accumbens Cell-Type Specific Deep Brain Stimulation in Cocaine Reinstatement

> **NIH NIH F32** · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · 2021 · $68,562

## Abstract

Project Summary/Abstract
Cocaine addiction is a major public health issue in the United States, and there are currently no effective
treatments targeted towards preventing relapse. Deep brain stimulation (DBS) has been successful clinically at
reducing symptoms of several neurological and psychiatric disorders and has been proposed as a potential
therapy for the suppression of drug craving and relapse. Previous preclinical research has identified that
conventional DBS in the nucleus accumbens (NAc) shell can be effective at preventing reinstatement of
cocaine seeking, an animal model of relapse. This grant will exploit recent methodological advances in order to
examine the cellular and physiological mechanisms underlying the efficacy of NAc DBS with greater specificity.
We will examine the effects of DBS-like stimulation induced by light activation of channelrhodopsin (ChR2)
expressed in specific neuronal subtypes of the NAc shell. Neuronal specificity will be achieved through viral
expression in transgenic rat lines that express Cre recombinase selectively in D1 dopamine receptor (D1DR)-
or D2DR-expressing medium spiny neurons (MSNs). Aim 1 will examine the electrophysiological effects of
optogenetic DBS-like (opto-DBS) activation of D1DR- or D2DR-MSNs in male and female rats. Whole cell
patch clamp experiments will assess the synaptic mechanisms that are engaged by opto-DBS, and determine
if there are cell subtype-specific effects. Aim 2 will consist of parallel behavioral experiments to examine the
effects of opto-DBS on cocaine-primed reinstatement. Optic fibers will be implanted in the NAc shell, and
D1DR- or D2DR-MSNs will be activated optogenetically, at DBS-like frequencies following a priming dose of
cocaine to assess the effects of this manipulation on cocaine-seeking behavior. Previous findings and
preliminary data support the overarching hypothesis that DBS of the NAc shell blocks cocaine-primed
reinstatement by inducing synaptic depotentiation specifically in D2DR-MSNs. Future directions will examine
the effects of selective optogenetic inhibition of D1DR- or D2DR-MSN signaling in precise downstream regions.
Optic fibers will be implanted in either the ventral pallidum (VP) or ventral tegmental area (VTA) and
halorhodopsin-expressing D1DR- or D2DR- axon terminals will be activated during cocaine-primed
reinstatement. This will determine whether DBS of NAc shell MSNs can be equated to overall suppression of
neural activity. Overall, identification of the specific mechanisms by which DBS influences cocaine seeking will
provide critical insights for future cell- and pathway-specific therapeutics for cocaine addiction.

## Key facts

- **NIH application ID:** 10314536
- **Project number:** 1F32DA052993-01A1
- **Recipient organization:** RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
- **Principal Investigator:** Matthew T Rich
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 1
- **Project period:** 2022-01-08 → 2023-01-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314536

## Citation

> US National Institutes of Health, RePORTER application 10314536, Mechanisms of Nucleus Accumbens Cell-Type Specific Deep Brain Stimulation in Cocaine Reinstatement (1F32DA052993-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10314536. Licensed CC0.

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