# PHARMACOLOGICAL ANTAGONISM AND GENETIC MANIPULATION OF CANNABINOID CB1 RECEPTORS IN THE AMYGDALA TO REDUCE PROTRACTED ETHANOL CONSUMPTION

> **NIH NIH F30** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $51,752

## Abstract

Project Summary/Abstract
 Alcohol Use Disorder (AUD) is a widespread problem with significant health and societal
consequences and a need for improved treatments. The endogenous cannabinoid system is a
promising target for new AUD pharmacotherapy. Prolonged ethanol consumption leads to
molecular and epigenetic changes in the amygdala underlying the negative affective state in
addiction. The amygdala has a high density of cannabinoid CB1 receptors. While cannabinoid
antagonists reduce ethanol drinking, their ability to alter molecular and epigenetic changes in the
amygdala remains unexplored. Furthermore, neutral cannabinoid receptor antagonists possess
less psychiatric liabilities than older inverse agonists such as rimonabant. This project exploring
cannabinoid receptor manipulations will provide evidence for a novel AUD pharmacotherapy and
characterize the epigenetic regulation of the endocannabinoid system in drinking behaviors.
 Despite indications neutral cannabinoid receptor antagonism reduces drug and ethanol
consumption, it is less clear how chronic ethanol drinking epigenetically impacts the
endocannabinoid system or how CB1 receptors in specific addiction-related brain circuits such as
the extended amygdala regulate drinking behaviors. This proposal is based on the hypothesis
that modulation of the CB1 receptor system can reduce escalated ethanol drinking and
reverse alcohol-induced changes in gene expression and histone modifications in the
amygdala. We will test this hypothesis by assessing AM4113 effects on drinking behavior and
biochemical changes in amygdalar endocannabinoid system gene expression and global and
specific Cnr1 (CB1 mRNA) histone modifications following intermittent-access 20% ethanol
drinking. We will further test the effect of Cnr1 knockdown within the central and basolateral nuclei
of the amygdala on protracted drinking behavior to specifically localize sub-regions of the
amygdala as sufficient for these same downstream behavioral and biochemical effects. Overall,
these experiments will further the understanding of the endocannabinoid system and its
epigenetic regulation during protracted ethanol drinking while providing key preclinical data for
translating endocannabinoid-targeted treatments for AUD.

## Key facts

- **NIH application ID:** 10380565
- **Project number:** 5F30AA027936-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Russell Scott Dulman
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2020-04-15 → 2023-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380565

## Citation

> US National Institutes of Health, RePORTER application 10380565, PHARMACOLOGICAL ANTAGONISM AND GENETIC MANIPULATION OF CANNABINOID CB1 RECEPTORS IN THE AMYGDALA TO REDUCE PROTRACTED ETHANOL CONSUMPTION (5F30AA027936-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380565. Licensed CC0.

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