# The Role of GSK3B in Progressive Alcohol Consumption

> **NIH NIH F31** · VIRGINIA COMMONWEALTH UNIVERSITY · 2022 · $39,901

## Abstract

Project Summary
Alcohol Use Disorder (AUD) is a major public health problem within the United States. Alcohol is the third
leading cause of preventable death in the country and nearly 6% of the adult population meets criteria for an
AUD. Unfortunately, due to the complex relationship between genetics and environment which contribute to the
development of AUD, the mechanisms behind its etiology remain unclear. This project aims to elucidate the
role of glycogen synthase kinase 3 beta (GSK3B) in modulating ethanol behaviors. Previous research has
revealed Gsk3b to be a hub gene in a network highly regulated by ethanol in the mouse medial prefrontal
cortex (mPFC). In response to acute ethanol, GSK3B undergoes inhibitory phosphorylation in both the mPFC
and nucleus accumbens (NAc). Additionally, studies on rodent drinking behavior have demonstrated
pharmacological inhibition of GSK3B decreases ethanol consumption. Gene targeting studies have further
implicated GSK3B in an ethanol-response pathway, showing knock-out decreases ethanol consumption while
overexpression produces an increase. The exact cell type specificity behind this response is yet unknown,
however evidence suggests deletion of GSK3B within CamKIIa+ cells of the entire forebrain is capable of
decreasing drinking behavior. This proposal seeks to increase our knowledge on the critical cell type behind
this response by more specifically targeting CamKIIa+ cells exclusively within the mPFC. Additionally, it is our
hypothesis that GSK3B’s response to ethanol occurs within a circuit between the NAc and PFC to regulate
ethanol behaviors. Finally, we seek to investigate how adaptations of the GSK3B response within this circuit
during the shift from acute ethanol exposure to chronic drinking may be contributing to the development of
progressive ethanol consumption.

## Key facts

- **NIH application ID:** 10466065
- **Project number:** 1F31AA030216-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Samantha Ann Gottlieb
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,901
- **Award type:** 1
- **Project period:** 2022-05-25 → 2025-05-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10466065

## Citation

> US National Institutes of Health, RePORTER application 10466065, The Role of GSK3B in Progressive Alcohol Consumption (1F31AA030216-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10466065. Licensed CC0.

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