# Mu-opioid receptors in the habenulo-interpeduncular circuit in opioid dependence

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $237,000

## Abstract

PROJECT SUMMARY
Withdrawal is a major obstacle in overcoming opioid dependence and addiction. Identifying the neural circuits
involved and how opioids modulate their activity is essential for developing new therapeutic strategies. The
medial habenula (MHb) expresses particularly high levels of mu-opioid receptor (MOR) and emerging evidence
implicates the MHb as a hotspot for the physical and affective symptoms of opioid withdrawal and relapse.
Despite this, there is remarkably little information on how MOR signaling influences MHb projection neurons, or
how chronic MOR signaling could induce physiological changes in MHb circuits that contribute to withdrawal.
MHb neurons project principally to the interpeduncular nucleus (IPN) where they can release acetylcholine (ACh)
or glutamate; and some of these neurons can co-release both glutamate and ACh. While cholinergic- and
glutamatergic-defined MHb neurons have been implicated in processes underlying addiction, the respective roles
and relative importance of these co-transmitters remain unclear. Based on prior literature and preliminary data
we posit an important role for glutamate and ACh co-release from MHb to IPN in mediating effects of opioid
dependence, including withdrawal. In this exploratory proposal we aim to test how acute and chronic MOR
activation influences activity in MHb and synaptic transmission in IPN and contributes to opioid dependence.

## Key facts

- **NIH application ID:** 10309782
- **Project number:** 1R21DA054693-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Thomas Hnasko
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10309782

## Citation

> US National Institutes of Health, RePORTER application 10309782, Mu-opioid receptors in the habenulo-interpeduncular circuit in opioid dependence (1R21DA054693-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10309782. Licensed CC0.

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