# Alcohol-related suppression of GIRK channel activity in the basal amygdala: a link to plasticity of glutamatergic neurotransmission and withdrawal-associated behavior?

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $338,953

## Abstract

PROJECT SUMMARY
Repeated cycles of alcohol intoxication and withdrawal foster adaptations in brain regions that regulate mood,
learning, and goal-directed behavior. These adaptations are thought to promote heightened anxiety, cognitive
deficits, and craving – hallmarks of alcohol use disorder (AUD) that collaborate to promote compulsive drug-
seeking behavior, increase relapse susceptibility, and impede the development of adaptive behaviors that
could support abstinence. Although treatment options for AUD are limited, preclinical and clinical data have
generated interest in the GABAB receptor (GABABR) as a potential target for therapeutic interventions aimed at
diminishing craving and reducing alcohol intake. The focus of this project is on an ethanol-induced
adaptation in GABABR-dependent signaling in the basal amygdala – a key substrate of anxiety as well as
learning related to rewards and aversive experiences. Using two distinct ethanol exposure models that yield
repeated cycles of intoxication, we found that somatodendritic GABABR-dependent signaling is suppressed in
principal neurons of the mouse BA, as measured 3-4 days after the last ethanol exposure. The adaptation is
not seen in principal neurons of the lateral amygdala or pyramidal neurons of the medial prefrontal/prelimbic
cortex, nor is it evoked by repeated cocaine. The adaptation is attributable to a suppression of G protein-gated
inwardly rectifying K+ (GIRK) channel activity, a known determinant of anxiety-related behavior and associative
learning. The goal of this project is to understand the salient features and mechanisms, as well as
neurophysiological and behavioral implications, of the ethanol-induced suppression of GIRK channel activity in
BA principal neurons. The two interrelated AIMs are to: (1) Elucidate mechanisms underlying the ethanol-
induced suppression of GIRK channel activity. Proposed studies will employ techniques in ex vivo
electrophysiology, immunoelectron microscopy, and neuron-specific viral manipulations to test the hypothesis
that the ethanol-induced suppression of GIRK channel activity in BA principal neurons is mediated by the
GIRK3 subunit-dependent internalization of GIRK channels. (2) Understand the downstream
neurophysiological and behavioral implications of GIRK channel plasticity. Proposed studies will probe the
implications of the suppression of GIRK channel activity in BA principal neurons, testing the hypothesis that it
is sufficient to provoke adaptations in glutamatergic neurotransmission in discrete BA projections. In parallel,
the consequences of the adaptation to anxiety-related behavior, associative (fear) learning, and voluntary
ethanol consumption will be evaluated in ethanol-naïve mice, following viral genetic suppression of GIRK
channel activity in BA principal neurons. Summary: This project leverages the complementary expertise of an
experienced team, and the availability of custom research tools, to investigate a previously undescrib...

## Key facts

- **NIH application ID:** 10109093
- **Project number:** 5R01AA027544-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** KEVIN D WICKMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $338,953
- **Award type:** 5
- **Project period:** 2020-02-20 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10109093

## Citation

> US National Institutes of Health, RePORTER application 10109093, Alcohol-related suppression of GIRK channel activity in the basal amygdala: a link to plasticity of glutamatergic neurotransmission and withdrawal-associated behavior? (5R01AA027544-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10109093. Licensed CC0.

---

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