# Opioid-induced changes to cannabinergic regulation of dopamine and motivation during protracted withdrawal

> **NIH NIH F99** · MARQUETTE UNIVERSITY · 2021 · $31,156

## Abstract

PROJECT SUMMARY
Opioid abuse remains a costly epidemic in the US, prompting research into new and effective interventions to
curb addiction-like behavior. Amongst the therapeutic characteristics of opioids, their associated withdrawal
effects are substantial and recognized to contribute to development of abuse and relapse. While acute somatic
withdrawal symptoms are relatively well characterized, their prolonged affective counterparts are less
understood. Regulating a broad array of affective behaviors, the mesolimbic dopamine (DA) system has been
demonstrated as both necessary and sufficient for reward-related behavior towards opioids and withdrawal-
related negative affect, with a canonical hypodopaminergic state following opioid dependence at least partially
responsible for drug craving and relapse vulnerability. Despite this, limitations of previous studies concerning
heterogeneity of mesolimbic circuitry and a shortage of assessments of opioid-induced long-term changes to
motivated behavior and subsequent drug intake following dependence have stifled clear demonstrations of
protracted motivational dysfunction and detection of underlying mechanism for the associated hypodopaminergic
state. Growing evidence indicates that cannabinoid (CB) signaling is highly influential in regulating
mesoaccumbal dopamine and opioid systems, including dopamine and opioid control of reinforcement, and that
CB-based therapies may hold efficacy in treating negative affective states during acute/somatic withdrawal and
perhaps opioid intake. Despite these promising data, data regarding how CB signaling is altered during opioid
withdrawal and whether CB-therapies are efficacious in countering dependence-related changes in motivation
for and intake of opioids with more protracted withdrawal are almost non-existent. This proposal builds off my
research to date demonstrating that 1) morphine dependence promotes a long-lasting elevation in GABAA-
mediated inhibitory tone specific to DA neurons in the lateral ventral tegmental area projecting to the lateral
nucleus accumbens shell (latVTA-latShell), 2) prior dependence increases motivation for and intake of morphine,
and 3) elevations in GABA signaling align with an apparent tolerance to CB1-induced disinhibition of lateral VTA
DA firing. In Aim2/Exp1, I will utilize ex vivo slice electrophysiology to assess alterations in synaptic strength and
CB-dependent regulation of GABAergic afferents from the rostromedial tegmental nucleus (RMTg) to latVTA-
latShell DA cells. Behavior studies in Aim2/Exp2 will extend upon data demonstrating increased effort-based
motivated responding for morphine under protracted withdrawal conditions by measuring cannabinoid-induced
alteration of this effect. Completing these experiments will support my research development by adding technical
skills in more sophisticated electrophysiology and behavioral approaches. Further, results will fill critical
unknowns regarding mechanisms underlying oste...

## Key facts

- **NIH application ID:** 10319399
- **Project number:** 1F99NS124177-01
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** Devan Marc Gomez
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $31,156
- **Award type:** 1
- **Project period:** 2021-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10319399

## Citation

> US National Institutes of Health, RePORTER application 10319399, Opioid-induced changes to cannabinergic regulation of dopamine and motivation during protracted withdrawal (1F99NS124177-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10319399. Licensed CC0.

---

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