# Contribution of MCL memory circuits to opioid seeking in chronic pain

> **NIH NIH P50** · NORTHWESTERN UNIVERSITY · 2022 · $284,402

## Abstract

Opioid drugs are widely prescribed to patients suffering from chronic pain despite the fact that we still
know very little about the impact of opioids, chronic pain, and both conditions on brain function. The main
goals of this project are to (i) provide novel evidence for the functional interaction between reward-, pain-, and
memory-processing circuits, (ii) determine how this interaction is affected by chronic pain, and (iii) show
whether restoring the function of these circuits can reduce pain and opioid addiction. Based on our recent and
pilot studies, we posit that functional changes in projections from the mesolimbic ventral tegmental area (VTA)
to DH, carrying information on pain and reward, alter hippocampal plasticity and enable the DH-RSC memory
circuit to gain excessive control over both chronic pain and opioid craving. Dissecting the role of individual
neurotransmitter circuits is essential for the better understanding of sex-specific differences in opioid seeking,
showing higher susceptibility of females to aversive triggers and higher susceptibility of males to rewarding
triggers. Specific Aim 1 is designed to determine the role of VTA-DH projections in chronic pain and opioid
craving using chemogenetic inactivation of glutamatergic, GABAergic, dopaminergic pathways. Specific Aim 2
will use similar approaches to determine the role of glutamatergic DH-RSC and RSC-VTA projections.
Specific Aim 3 will show whether sex-specific activity of discrete VTA-DH-RSC projections is sufficient to
induce pain and opioid craving. Specific Aim 4 will integrate key findings of Project 3 with findings of the other
projects of the Center by examining the relationship between memory and reward circuits (Project 2), the
relationship between transcriptional changes in the VTA and the reorganization of VTA-DH circuits (Project 4),
the impact of individual VTA-DH-RSC pathways on whole brain activity and connectivity (Project 1), and the
relevance of our findings for patient populations (Project 1). We expect to show that originally distinct
pathways processing pain, reward, and memory, alter their stimulus specificity during chronic pain and
addiction, causing changes of DH plasticity and reorganization of the VTA-DH-RSC circuit. The circuit,
transcriptional, and synaptic mechanisms identified in this project will serve as a basis for development of new
treatments for chronic pain and addiction.
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## Key facts

- **NIH application ID:** 10440296
- **Project number:** 5P50DA044121-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jelena Radulovic
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $284,402
- **Award type:** 5
- **Project period:** 2018-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440296

## Citation

> US National Institutes of Health, RePORTER application 10440296, Contribution of MCL memory circuits to opioid seeking in chronic pain (5P50DA044121-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440296. Licensed CC0.

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