# Molecular Basis for Structural and Behavioral Effects of Chronic Opioid Exposure

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2021 · $50,037

## Abstract

PROJECT SUMMARY
 Opioid addiction is a chronic relapsing disease affecting at least 2 million Americans with an associated
annual mortality approaching 50,000 deaths. Currently available interventions have proven ineffective in
addressing this public health crisis. Over the past several decades, significant progress has been made in
identifying the neural mechanisms of opioids. Like other drugs of abuse, opioids activate the mesolimbic
dopamine pathway, increasing the excitability of dopaminergic neurons in the ventral tegmental area (VTA)
and enhancing dopamine neuromodulation via projections to a variety of targets. The effects of mesolimbic
dopamine activation in mice are well studied and include heightened locomotor activity. One VTA target, the
nucleus accumbens (NAc), is thought to act as a “rheostat” of reward, and fluctuations in dopamine release in
this region appear to control whether stimuli are perceived as rewarding or aversive. Beyond acute effects,
repeated administration of opioids demonstrates that these drugs are capable not only of modifying dopamine
release but also of inducing plasticity in the dopamine response. For example, in a phenomenon known as
psychomotor sensitization, repeated exposure to a fixed dose of opioid produces a progressive increase in
locomotion. As a neural correlate of sensitization, opioids are known to induce alterations in the density of
synaptic contacts onto the dominant neuronal population in the NAc, medium spiny projection neurons
(MSNs). These changes likely modify the internal circuit dynamics of the NAc to accentuate drug reward and
reinforcement, contributing to the development addiction and relapse. However, a dearth of knowledge
concerning opioid-induced changes to the microcircuitry of key neural reward substrates presents a
significant barrier to the rational design of therapies aimed at preventing opioid-induced synaptic
rewiring. MSNs are heterogenous, consisting of at least two subpopulations, distinguishable by their
expression of the D1-dopamine receptor or the D2-dopamine receptor. D1-MSNs appear to promote addictive
behaviors while D2-MSNs may oppose these behaviors. Despite the functional significance of these
differences, the cell-type specificity of opioid-induced morphologic changes has not been investigated. The
proposed experiments will examine subtype-specific structural plasticity of excitatory and inhibitory synapses
onto MSNs in the NAc in response to repeated morphine exposure. We will then evaluate the same
parameters in a mutant known to exhibit attenuated psychomotor sensitization to determine whether subtype-
specific spine changes by this mutation.

## Key facts

- **NIH application ID:** 10209941
- **Project number:** 5F30DA052109-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Dieter Brandner
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $50,037
- **Award type:** 5
- **Project period:** 2020-06-24 → 2024-06-23

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209941

## Citation

> US National Institutes of Health, RePORTER application 10209941, Molecular Basis for Structural and Behavioral Effects of Chronic Opioid Exposure (5F30DA052109-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10209941. Licensed CC0.

---

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