# Involvement of Cortical Excitatory Projections in Cocaine Addiction

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $671,981

## Abstract

PROJECT SUMMARY / ABSTRACT
There is no effective clinical treatment to prevent relapse to psychostimulants, although extensive studies have
been done focusing on the medial prefrontal cortex and nucleus accumbens. Breakthroughs in the clinical
settings rely heavily on a better understanding of brain adaptations, which may explain both chronic drug seeking
and taking behaviors. Persistent drug seeking behaviors after a prolonged withdrawal period, as the most
accepted laboratory animal model in predicting the risk of relapse, is not exclusively motivation-driven. Here we
propose that by the passage of the withdrawal period, the motor/habit components of drug seeking behaviors
increase and gradually take over the initial motivational components. The cortical pyramidal neurons (CPNs) in
the Supplementary Motor Cortex (M2) will be the central focus of this proposal. Our hypothesis is that high
excitability in M2 CPNs and enhanced glutamate release at the M2 CPN terminals in the striatum lead to high
drug seeking behaviors at later withdrawal stages after cocaine exposure. Three specific Aims are proposed to,
first, examine the excitability of CPNs in the M2 region (Aim 1) and the excitatory transmission in the M2-DLS
projection (Aim 2), and then to prevent cocaine seeking (Aim 3) in Sprague Dawley (SD) rats with a history of
intravenous self-administration of cocaine. Mechanisms of relapse will be investigated in the motor CPNs in the
M2 area and their target dorsolateral striatal synapses. Our hope is to pave the way not only to provide an original
perspective in our understanding of addiction-like behaviors, but also to propose novel targets for clinical
management of drug relapse.

## Key facts

- **NIH application ID:** 10890218
- **Project number:** 1R01DA059548-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Yao-Ying Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $671,981
- **Award type:** 1
- **Project period:** 2024-09-30 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890218

## Citation

> US National Institutes of Health, RePORTER application 10890218, Involvement of Cortical Excitatory Projections in Cocaine Addiction (1R01DA059548-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10890218. Licensed CC0.

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