# Molecular Signatures of Social Stress-Induced Escalation of Drinking

> **NIH NIH R21** · LSU HEALTH SCIENCES CENTER · 2024 · $189,159

## Abstract

Social stress is one of the most common forms of stress experienced by humans and has been well documented
to contribute to a wide variety of neuropsychiatric conditions. Exposure to repeated social defeat stress (SDS)
in rodents enhances the rewarding and reinforcing effects of several drugs of abuse, including alcohol, and is a
reliable predictor of future drug use. SDS is effectively modeled in animals through social defeat paradigms,
where an antagonistic encounter is initiated between two animals of the same species. There is substantial
overlap between brain regions that mediate the behavioral response to stressors and those that mediate drug
addiction, implying shared neural circuitry. However, the precise neural mechanisms by which social stressors
increase alcohol consumption are not well understood. This application will address this gap in knowledge by
using a cell type agnostic approach to identify and profile the transcriptomes of cells that are activated by both
SDS and alcohol exposure at single cell resolution. Using the recently developed TRAP2 (Targeted
Recombination in Activated Populations) system and a mouse model for SDS-induced escalation of alcohol
drinking, we examined the overlap between neural ensembles that are activated by social stress and alcohol
consumption in the same animal. Our preliminary results indicate that SDS increased alcohol consumption and
neuronal activation in the paraventricular thalamus (PVT) and the paraventricular nucleus of the hypothalamus
(PVN), brain regions known to mediate the motivational effects of stress. We found that both stress and alcohol
by themselves activate a large number of cells in the PVT and PVN. Interestingly, our results also indicate that
>80% of stress-activated cells are also activated by alcohol in these brain regions. Based on these results, we
hypothesize that transcriptional programs in cells that are activated by both stress and alcohol in the PVT and
PVN are unique compared to those that are activated by stress alone or alcohol alone and underlie stress-
induced escalation of alcohol consumption. We propose to use single nuclei sequencing to transcriptionally
profile cells in the PVT and PVN that are activated by both stress and alcohol. We will then identify genes,
pathways and processes that are dysregulated in these cells. We also propose to us the Library of Integrated
Cellular Signatures (LINCs) to identify compounds that will reverse these transcriptional signatures and are thus
predicted to prevent stress-induced escalation of alcohol consumption.

## Key facts

- **NIH application ID:** 10843152
- **Project number:** 5R21AA030652-02
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Rajani Maiya
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $189,159
- **Award type:** 5
- **Project period:** 2023-05-20 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843152

## Citation

> US National Institutes of Health, RePORTER application 10843152, Molecular Signatures of Social Stress-Induced Escalation of Drinking (5R21AA030652-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10843152. Licensed CC0.

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