# Regulation of alcohol-induced social disturbances by lateral habenula serotonin receptors

> **NIH NIH R00** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $249,000

## Abstract

The COVID-19 pandemic has greatly exacerbated rising patterns of excessive alcohol consumption, particularly
in women. Binge alcohol drinking is the most common pattern of excessive alcohol drinking and is associated
with increased risk of developing mood disorders and Alcohol Use Disorder (AUD). Social support strongly
buffers against alcohol craving and relapse, yet many individuals display reduced valuation of social rewards
and/or deficits in the processing of social stimuli following alcohol exposure and subsequent abstinence. This
may compound interpersonal problems in people with AUD and limit their capacity to seek out or receive social
support. Therefore, understanding the neurobiological mechanisms mediating alcohol’s effects on social
behavior is required to inform future treatments aimed at enhancing social functioning and reducing relapse in
patients with AUD. Drinking in the Dark (DiD) is a robust paradigm for investigating the circuit and molecular
mechanisms of binge-like alcohol consumption on physiology and behavior in rodents. In addition, the 3-chamber
sociability model permits the interrogation of both social reward and social recognition behaviors following
alcohol consumption. Serotonin (5-Hydroxytryptamine, 5-HT) receptor signaling in the lateral habenula (LHb)
has been implicated in the development of negative emotional states associated with abstinence from alcohol,
but the LHb remains highly understudied in the context of AUD. I recently found that DiD reduced social
recognition selectively in female mice during abstinence, and that genetic deletion of the LHb Gq-protein coupled
serotonin receptor 5HT2c partially prevented this effect. My preliminary data suggests that binge alcohol
consumption enhances the intrinsic excitability of LHb 5HT2c-containing neurons (LHb5HT2c) in the medial sub-
region, that 5-HT is released onto LHb5HT2c during social interaction, and that acute engagement of Gi signaling
in LHb5HT2c can normalize social deficits induced by alcohol. Moreover, DiD appears to modulate the expression
of multiple 5-HT receptor subtypes co-expressed in LHb5HT2c. Together, these data suggest that excessive
activation of LHb5HT2c via dysregulation of 5-HT receptor signaling may underlie social deficits induced by alcohol.
Using these preliminary findings as a foundation for the current proposal, I will 1) characterize how DiD alters
the translational and physiological landscape of LHb5HT2c projecting to the DRN (5HT2cLHb-DRN) and 2) investigate
the functional impact of genetic manipulation of 5-HT receptor sub-types in 5HT2cLHb-DRN on neuronal physiology
and DiD-induced dysregulation of social behavior. Together, these experiments will determine the effects of
binge alcohol drinking on molecular and physiological processes in 5HT2cLHb-DRN and identify novel mechanisms
by which these neurons promote social dysfunction during abstinence. Furthermore, this award will provide me
with valuable technical and professiona...

## Key facts

- **NIH application ID:** 11160202
- **Project number:** 4R00AA030628-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Meghan Elizabeth Flanigan
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-08-25 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11160202

## Citation

> US National Institutes of Health, RePORTER application 11160202, Regulation of alcohol-induced social disturbances by lateral habenula serotonin receptors (4R00AA030628-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11160202. Licensed CC0.

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