# Effects of cocaine taking and seeking on histone deacetylase class IIa enzyme activity in the nucleus accumbens of rats

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $590,447

## Abstract

Project Summary / Abstract
 Cocaine addiction is a debilitating mental health disorder that interferes with an individual’s well-being,
disrupts relationships, and burdens society. Cocaine, like other drugs of abuse, hijacks the brain’s reward
center, producing enduring changes in brain regions, such as the nucleus accumbens (NAc), that perpetuate
the cycle of addiction. Preclinical studies show that cocaine and other psychostimulants act as general
enhancers of gene expression and that histone deacetylases (HDACs) in the NAc play a key role in the
development of cocaine addiction. However, neurobiological understanding of the role of specific HDACs in
these processes is limited and there are few in vivo studies on these targets. In response to the need for such
studies, this proposal integrates state-of-the-art small animal positron emission tomography (PET) techniques
with a model of cocaine self-administration (coc-SA) to study the role of NAc HDAC Class IIa (HDAC5)
enzymatic activity during cocaine taking and seeking behaviors. The combination of in vivo neuroimaging and
behavioral neuroscience methods in a longitudinal (repeated-measures) design presents an opportunity to
advance understanding of the role of epigenetic activity in the NAc during the 4 phases of coc-SA, including
acquisition, maintenance, extinction, and reinstatement. Our overall hypothesis is that cocaine will
decrease the enzymatic activity of HDAC Class IIa proteins in the NAc, which will statistically
explain increases in cocaine taking and seeking behaviors. Three aims will test this hypothesis. (1)
Determine HDAC Class IIa enzymatic activity in the NAc using PET imaging and a novel substrate-based PET
ligand at baseline and during the phases of coc-SA. (2) Determine the changes in HDAC Class IIa enzymes and
protein targets in the NAc at the different phases of coc-SA using immunohistochemistry. (3) Determine the
effect of nuclear HDAC5 in the NAc on class IIa HDAC enzymatic activity during cocaine seeking behavior.
The combination of non-invasive PET assays with behavioral neuroscience methods to study the role of
HDAC Class IIa enzyme activity in the NAc during cocaine taking and seeking behaviors provides a
unique strategy to study the neurobiological mechanisms that underlie the stages of addiction. The
proposed studies of this application will deliver translational knowledge that addresses theoretical and
neurobiological gaps in our understanding of the role of epigenetics in cocaine addiction. This
knowledge will aid in the development of novel neurotherapeutics that target epigenetic regulators
and treat this devastating mental health disorder.

## Key facts

- **NIH application ID:** 9978025
- **Project number:** 5R01DA042057-04
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Shane Alan Perrine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $590,447
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978025

## Citation

> US National Institutes of Health, RePORTER application 9978025, Effects of cocaine taking and seeking on histone deacetylase class IIa enzyme activity in the nucleus accumbens of rats (5R01DA042057-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978025. Licensed CC0.

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