# Modulation of the Perineuronal Net Protein Brevican in the Nucleus Accumbens, and its Impact on Addiction-related Behavior

> **NIH NIH F31** · DUKE UNIVERSITY · 2020 · $37,551

## Abstract

Project Summary
Psychostimulant drugs of abuse induce persistent functional changes in the neural reward circuitry that
underlie the development of addiction. These regions include the nucleus accumbens (NAc), a key area for
drug reward. Growing evidence suggests that altered interneuron function in NAc makes key contributions to
the drug-induced circuit adaptations leading to addiction behaviors. We have shown that NAc parvalbumin-
expressing (PV+) inhibitory interneurons are required for multiple addiction-related behaviors in mice, including
amphetamine (AMPH)-induced locomotor sensitization and conditioned place preference (CPP). Others have
shown that cocaine self-administration strengthens excitatory inputs from basolateral amygdala onto NAc PV+
interneurons, and artificially potentiating these synapses accelerates acquisition of cocaine self-administration
in naïve mice, suggesting that synaptic plasticity in NAc PV+ interneurons is behaviorally relevant for the
development of addiction-like behaviors. However, little is known about the molecular mechanisms by which
psychostimulants alter PV+ inhibitory interneuron function, and how this contributes to addictive behaviors. A
promising mechanistic target is the perineuronal net protein Brevican (Bcan), which plays a cell-autonomous
role in stabilizing excitatory inputs onto PV+ interneurons. The overarching goal of this proposal is to test the
hypothesis that repeated psychostimulant exposure modulates PV+ interneuron activity through regulation of
Bcan expression. In Aim 1 I will characterize the regulation of Bcan expression in NAc PV+ interneurons over
the development of AMPH CPP. In Aim 2 I will test how manipulating Bcan expression affects the synaptic
inputs to these neurons. In Aim 3 I will test the effect of manipulating Bcan in NAc PV+ cells on the threshold
to develop CPP. These studies will investigate cellular transcriptional and synaptic plasticity mechanisms
within PV+ interneurons, and how they affect the expression of addiction-related behaviors.

## Key facts

- **NIH application ID:** 9990127
- **Project number:** 1F31DA049442-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Mariah F Hazlett
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,551
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990127

## Citation

> US National Institutes of Health, RePORTER application 9990127, Modulation of the Perineuronal Net Protein Brevican in the Nucleus Accumbens, and its Impact on Addiction-related Behavior (1F31DA049442-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990127. Licensed CC0.

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