# Alcohol exposure reverses fear conditioning-induced change in endocannabinoid signaling

> **NIH NIH F30** · LSU HEALTH SCIENCES CENTER · 2020 · $37,373

## Abstract

Alcohol exposure reverses fear conditioning-induced change in endocannabinoid signaling
Post-traumatic stress disorder (PTSD) is a severe anxiety disorder characterized by a cluster of symptoms
including intrusive memories and hyper-arousal and reactivity. Maladaptive fear learning is one of the possible
mechanisms underlying disease pathology. Endocannabinoids, lipid neuromodulators, control several
physiological processes such as memory and mood are found to be altered in PTSD patients. PTSD patients
exhibit lower circulating endocannabinoids and increased level of cannabinoid receptor 1. Hence, cannabinoid
receptor agonists have been used to alleviate symptoms of PTSD. Nearly half of patients suffering from PTSD
meet the criteria for alcohol use disorder (AUD). Alcohol exposure has been shown to increase
endocannabinoids in several areas of the brain. This raise the possibility that decrease in endocannabinoid
signaling is not only involved in PTSD, but may also cause alcohol reinforcement. Mounting evidence has
implicated cerebellum in fear learning, emotional learning, and reward. My preliminary results show that the fear
conditioning increases monoacyl glycerol (MAGL) activity increasing endocannabinoid degradation in the
cerebellum. In contrast, chronic alcohol exposure decreases MAGL activity. Our central hypothesis is that fear
conditioning elevates MAGL activity and reduces eCB tone, which promotes retention of fear memories, while
subsequent alcohol exposure reverses these changes in the cerebellum. Aim 1 investigate the mechanisms of
increased MAGL activity. Aim 2 will study the mechanisms by which alcohol exposure reduces MAGL activity
using depolarization suppression of excitation and enzyme activity assay. Aim 2 will also investigate the effect
of chronic alcohol exposure on fear memory retention. This study will provide mechanistic insight about PTSD
comorbid AUD, which may lead to development of new therapeutics for this comorbidity.

## Key facts

- **NIH application ID:** 10068158
- **Project number:** 1F30AA028178-01A1
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Muhammad A. Farooq
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,373
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10068158

## Citation

> US National Institutes of Health, RePORTER application 10068158, Alcohol exposure reverses fear conditioning-induced change in endocannabinoid signaling (1F30AA028178-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10068158. Licensed CC0.

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