# The influence of peroxisome proliferator-activated receptor gamma coactivator - 1 alpha (PGC-1a) on the nucleus accumbens during cocaine-self-administration

> **NIH NIH F32** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $44,260

## Abstract

Project Summary/Abstract
Addiction to drugs of abuse exacts massive economic and human costs upon society. Drug addiction is often
characterized by persistant drug seeking and vulnerability to relapse, which are huge barriers to addiction
treatment. Relapse can occur even after prolonged abstinence and is often preceded by robust drug craving
precipitated by exposure to drug-paired stimuli and environments. This psychological persistence in drug craving
and seeking is tied to neurobiological changes of natural reward related systems by drugs of abuse. However,
the cell type-specific molecular mechanisms by which neuroplasticity takes place following drug consumption is
incompletely understood. A growing body of work indicates mitochondrial health and regulation are important for
neuronal modifications associated with substance use disorders and psychiatric illness. Here, I aim to identify
how cocaine alters transcriptional regulation within D1- medium spiny neurons (D1-MSNs) via the
transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-
1α). Previous work and preliminary data show that cocaine increases PGC-1α expression specifically in D1-
MSNs, increases D1-MSN spine density, and increases the number of small mitochondria via increased
mitochondrial fission. Further, exogenously increasing PGC-1α exaggerates cocaine-related behaviors like
locomotor sensitization and conditioned place preference. Despite these findings, a causal link between PGC-
1α and the spine and mitochondrial changes observed in D1-MSNs after cocaine has not been demonstrated,
nor has the necessity of PGC-1α for the expression of cocaine seeking behavior been established. I hypothesize
that cocaine alters drug seeking behavior, MSN spine density, and mitochondrial morphology by increasing the
expression and function of PGC-1α, and that reducing the expression of PGC-1α in D1-MSNs will block this
cocaine-induced plasticity. The experiments of Aim 1 of this proposal will test this hypothesis. Further, in Aim 2,
I will determine what genes PGC-1α interacts with after cocaine self-administration using chromatin
immunoprecipitation. I will then specifically measure the expression of PGC-1α-targeted genes that are involved
in mitochondrial and spine plasticity in D1-MSNs after cocaine self-administration. Together, using cutting edge
behavioral and molecular techniques, these experiments will establish the importance of PGC-1α in cocaine-
induced molecular and cellular changes that mediate cocaine SA and seeking. These aims synthesize my
interest in molecular mediators of behavior, my sponsor’s expertise in dissecting cell-type selective gene
expression in the striatum, and the experience of the diverse faculty at the University of Maryland School of
Medicine to improve our understanding of the neuronal mechanisms mediating drug craving. This work will both
improve our potential to predict relapse vulnerability and identify effectiv...

## Key facts

- **NIH application ID:** 10137611
- **Project number:** 1F32DA052966-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Cali Ann Calarco
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,260
- **Award type:** 1
- **Project period:** 2021-09-02 → 2023-05-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137611

## Citation

> US National Institutes of Health, RePORTER application 10137611, The influence of peroxisome proliferator-activated receptor gamma coactivator - 1 alpha (PGC-1a) on the nucleus accumbens during cocaine-self-administration (1F32DA052966-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10137611. Licensed CC0.

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