# Opioid actions on the habenulo-peduncular circuit

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $562,014

## Abstract

PROJECT SUMMARY
Withdrawal is a major obstacle in overcoming opioid dependence and addiction. Identifying the neural circuits
involved and how opioids modulate the activity of those circuits is essential for developing new therapeutic
approaches to prevent or treat opioid use disorder. The medial habenula (MHb) projects primarily to the
interpeduncular nucleus (IPN) and has long been known to express high levels of the Mu-opioid receptor (MOR).
Activity in this circuit has been associated with expression of fear and anxiety; and repeatedly implicated in
mediating aversive qualities of nicotine and nicotine dependence. Emerging evidence also supports a role for
MHb projections to IPN in the somatic and affective symptoms of opioid withdrawal. Despite this, there is
remarkably little information on what cell types in both MHb and IPN express MOR, how MOR signaling
influences this circuit, and whether chronic MOR signaling induces physiological changes in this circuit that
contribute to withdrawal. In this proposal we propose experiments to inform each of these questions using a
combination of molecular, physiological, and behavioral approaches to investigate MOR-expressing neurons in
both MHb and IPN of mice. Based on prior literature and preliminary data we posit an important role for excitatory
neurons in lateral MHb and inhibitory neurons in rostral IPN in mediating aversive qualities of opioid dependence
that contribute to withdrawal and relapse.

## Key facts

- **NIH application ID:** 10942537
- **Project number:** 1R01DA060923-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Thomas Hnasko
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $562,014
- **Award type:** 1
- **Project period:** 2024-09-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10942537

## Citation

> US National Institutes of Health, RePORTER application 10942537, Opioid actions on the habenulo-peduncular circuit (1R01DA060923-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10942537. Licensed CC0.

---

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