# Fast-spiking interneurons in the Nucleus Accumbens and cue-induced cocaine seeking

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $45,520

## Abstract

Abstract
Drug addiction is a prominent medical and social problem with no effective treatments. The malfunction of the
nucleus accumbens (NAc) has been identified to critically contribute to the development of addiction and
related behaviors. To understand the drug-induced functional alterations in the NAc contributing to addiction,
extensive efforts have been spent investigating NAc medium spiny neurons (MSNs), which constitute over
90% of NAc neurons and directly mediate the output of the NAc. In contrast fast-spiking interneurons (FSIs)
have largely been ignored. While FSIs only constitute a very small portion of NAc neurons (<1%), our
preliminary results show that FSIs within the NAc provide robust inhibition to MSNs in response to specific
excitatory inputs, gating MSN activity and in turn shaping the functional output of the NAc. This regulation
allows FSIs the capacity to greatly influence behaviors mediated by the NAc, including those associated with
addiction. The objective of this application is to determine the role of FSIs in mediating addiction-related
behaviors, using a clinically relevant rodent model of cue-induced cocaine seeking. Our preliminary studies
have found that upon exposure to cocaine-associated cues following abstinence from cocaine self-
administration, FSIs display a transient increase in activity while MSNs are simultaneously suppressed. This
timing-contingent cue-induced activity pattern and other results lead us to hypothesize!that the local FSI-MSN
connection dictates the output of NAc by controlling the activation of MSNs to promote cue-induced cocaine
seeking after abstinence. We will test this hypothesis by pursuing two aims. Our Aim 1 will thoroughly
characterize the cellular and circuit properties of FSI-mediated regulation of MSNs within the NAc to
understand the mechanistic and functional dynamics of this circuit in gating the functional output of the NAc to
influence behavior. Our Aim 2 will directly test the hypothesis that cue-induced FSI activity gates MSNs within
the NA to promote cue-induced cocaine seeking after withdrawal from cocaine self-administration. The
expected outcomes will provide a new conceptual basis in understanding how information is integrated and
computed within the NAc to shape addiction-related behaviors by introducing FSIs as critical components
within the NAc circuit. This information may provide new avenues for the development of novel therapeutic
strategies that target this small neural population for the treatment of addiction. As such, this proposal is highly
relevant to the mission of NIDA and NIH.

## Key facts

- **NIH application ID:** 9918319
- **Project number:** 5F31DA043940-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** William James Wright
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918319

## Citation

> US National Institutes of Health, RePORTER application 9918319, Fast-spiking interneurons in the Nucleus Accumbens and cue-induced cocaine seeking (5F31DA043940-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9918319. Licensed CC0.

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