# Heroin-induced plasticity: the role of actin dynamics

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $357,703

## Abstract

ABSTRACT
Opiate use, dependence, and addiction have dramatically increased to epidemic proportions in recent years.
This is a reflection of the increased misuse of prescription opioids and abuse of illegal opiate drugs, such as
heroin. Unfortunately, there are still relatively few effective pharmacotherapeutic interventions available for the
treatment of substance abuse and addiction, most of which rely on a replacement therapeutic model.
 Neuronal plasticity is considered to be a substrate that mediates the long-lasting changes in the brain's
reward circuit and a key component of the long-term addiction disease state. These neural adaptations occur in
brain regions such as the nucleus accumbens and lead to long-term drug craving and drug relapse. Currently,
there is a scarcity of mechanistic evidence that explores the molecular mechanisms of heroin-induced structural
plasticity. The overarching focus of this proposal is to determine the functional cellular neurobiological
mechanisms of heroin-induced behavioral plasticity.
 The proposed studies investigate the role of actin dynamics mediated through the actin-binding protein
drebrin in heroin-induced plasticity, ultimately resulting in long-term drug craving and relapse behaviors. To this
end, we have proposed three Specific Aims that will test the following hypotheses: to determine if heroin self-
administration results in a persistent and epigenetically-mediated decrease in the actin-stabilizing protein
drebrin, which in turn regulates actin turnover (Aim I); to determine that drebrin is an essential molecular
mechanism underlying heroin-induced relapse-like behaviors and structural plasticity following abstinence from
heroin self-administration (Aim II); and to determine if drebrin mediates drug seeking and structural plasticity in
D1- and in D2-expressing medium spiny neurons following heroin self-administration (Aim III).
 This application presents an opportunity to determine, for the first time, a causal mechanism—drebrin—in the
underlying cellular (actin dynamics; D1/D2 MSN cellular specificity), structural (morphological), and behavioral
(reinstatement) plasticity induced by heroin. The findings from the work in this application will elucidate
mechanisms by which chronic heroin exposure induces long-term changes in the plasticity of nucleus
accumbens neurons and provides new directions for the development of novel therapies for heroin addiction.

## Key facts

- **NIH application ID:** 10086970
- **Project number:** 5R01DA046818-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** DAVID M DIETZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $357,703
- **Award type:** 5
- **Project period:** 2019-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086970

## Citation

> US National Institutes of Health, RePORTER application 10086970, Heroin-induced plasticity: the role of actin dynamics (5R01DA046818-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10086970. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*