# Cellular signaling in alcoholism

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2021 · —

## Abstract

Alcohol use disorder (AUD) is a major health concern in the VA population as well as in the general population.
An integral part of the mission of the VA is to provide care for VA patients suffering from alcohol and/or drug
abuse problems. Cessation of chronic ethanol consumption leads to development of negative withdrawal
symptoms that promote increased alcohol drinking and maintain alcohol addictive behaviors. Amygdaloid brain
structures are known to play an important role in anxiety behaviors as well as in alcohol addiction. The
molecular mechanisms, and particularly the role of non-coding microRNAs (miRNAs; 21-23 nt), in specific
neural circuits of the brain that are involved in the development of anxiety-like behaviors during ethanol
withdrawal after chronic ethanol exposure are not well understood. Using microarray analysis, we recently
reported that acute ethanol exposure produces differential miRNA expression in the amygdala. This data
revealed that expression of miRNA-494 (miR-494) was decreased by acute ethanol exposure and its target
gene mRNA levels were increased and involved in the regulation of anxiolytic effects of ethanol. This proposal
will extend these studies and establish the role of miR-494 in the regulation of chromatin and synaptic
remodeling in the amygdala, leading to negative affective state of alcoholism. In addition, this proposal will
identify changes in the expression of other miRNAs during alcohol dependence and then propose experiments
to investigate how these changes in miRNAs coordinate shifts in the expression of target gene pathways that
regulate anxiety-like behaviors during withdrawal after chronic ethanol exposure. We hypothesize that
ethanol withdrawal after chronic exposure will produce differential expression of several miRNAs, and
one of these may be miR-494. The upregulation of miR-494 will induce changes in target genes that
regulate synaptic plasticity and dendritic spines in the amygdala which may underlie the development
of anxiety-like behaviors during ethanol withdrawal. The specific aims of the proposal are: 1) To perform
miRNA expression profiling using a microarray approach in the amygdala of rats during ethanol withdrawal
after chronic ethanol exposure. The emerging miRNAs will be validated and changes in the expression of their
putative target genes will also be examined. 2) To examine if a) miR-494 antagomir infusion in the CeA or
acute ethanol challenge will attenuate anxiety-like behaviors, deficits in the expression (mRNA and protein) of
direct targets (Cbp, p300, Cited2) and indirect targets (Bdnf, Arc, and synaptophysin) as well as deficits in
synapses and dendritic spines in the amygdala of rats during ethanol withdrawal after chronic ethanol
exposure and b) synthetic mimics of miR-494 infused into CeA of control rats will provoke anxiety-like
behaviors and reduce the expression of target genes in the amygdala. 3) To examine if the effects of CeA
infusion of a Cited2 siRNA in control ...

## Key facts

- **NIH application ID:** 10200664
- **Project number:** 5I01BX004517-03
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** SUBHASH C. PANDEY
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200664

## Citation

> US National Institutes of Health, RePORTER application 10200664, Cellular signaling in alcoholism (5I01BX004517-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10200664. Licensed CC0.

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