# Cortical Plasticity in Methamphetamine Addiction

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $355,063

## Abstract

Project Summary/Abstract
Many methamphetamine (meth) addicts suffer cognitive impairments that may perpetuate the addiction cycle.
Although, meth impacts several cognitive domains (e.g., attention, impulsivity, memory), the relationship
between impaired cognitive function, addiction, and relapse is not well understood. Repeated meth use results
in maladaptive brain changes in areas involved in recognition memory and relapse including cortical and
subcortical structures. For example, the perirhinal cortex (PRH) is the primary neural substrate involved in
recognition memory and directs the flow of information in and out of the parahippocampal structure. The medial
prefrontal cortex (mPFC) mediates inhibitory control over behaviors like risk-taking and drug over-consumption;
and, the nucleus accumbens (NA) regulates reward-related behaviors. Meth induced impairments in these
areas result in memory deficits, loss of inhibitory control, and biased reward processing of drug-associated
cues that precipitate a relapse episode. In this proposal, we will study the relationship between motivated drug
taking, meth induced cognitive dysfunction, and relapse using a long access (LA) meth self-administration (SA)
regimen that reliably establishes recognition memory deficits and results in robust relapse to drug seeking.
Given that the PRH is the primary substrate involved in recognition memory, combined with our previous
reports of a meth-induced dysregulation of glutamate physiology in this area, we hypothesis that meth impairs
recognition memory through PRH projection neurons loss of communication with the mPFC. We also suggest
that the pathway encompassing prelimbic (PL) and infralimbic (IL) outputs of the mPFC that project to the
NAcore and NAshell are dysregulated by meth resulting in the reinstated responding to conditioned drug cues.
As such these separate pathways, PRH-mPFC and mPFC-NA, suggest that recognition memory deficits and
relapse are distinct domains of the addiction pathology. However, the PRH-NAcore is a relatively unexplored
circuit and the behavioral relevance of this connection has not been determined. We hypothesize that this
connection may be the unifying pathway between meth-induced recognition memory dysfunction and relapse.
Our Specific Aims will determine whether meth causes functional changes within the pathways involved in
recognition memory and cued reinstatement. Specific Aim 1 will test the hypothesis that meth causes
functional changes within the PRH-mPFC circuitry that result in recognition memory deficits. Specific Aim 2
will test the hypothesis that functional changes within the mPFC-NA circuitry mediate cued reinstatement of
meth seeking using a rodent model of reinstatement. Specific Aim 3 will determine the functional and
behavioral relevance of the PRH-NAcore pathway. We hypothesize that this pathway is involved in recognition
memory and relapse to meth seeking. Upon completion of our aims we will have a more complete
un...

## Key facts

- **NIH application ID:** 9952343
- **Project number:** 5R01DA033049-08
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Carmela M Reichel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,063
- **Award type:** 5
- **Project period:** 2012-09-15 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952343

## Citation

> US National Institutes of Health, RePORTER application 9952343, Cortical Plasticity in Methamphetamine Addiction (5R01DA033049-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952343. Licensed CC0.

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