The University of Tennessee Health Science Center (UTHSC)
Project Title: Depression as a risk factor for enhanced alcohol use: insights from a rat model of voluntary alcohol consumption in a social setting
Mallory Udell is a neuroscience doctoral candidate at The University of Tennessee Health Science Center (UTHSC) working under Dr. Hao Chen in the Department of Pharmacology, Addiction Science, and Toxicology. She has been awarded the 2024 Innovative Student Research Grant to support her ongoing dissertation work, which focuses on examining how certain intrinsic factors modulate adolescent alcohol consumption using inbred rat models. Her project introduces a novel operant device, called HomeBrew, designed to allow rats to self-administer alcohol together as pairs. By simulating the social context in which humans typically consume alcohol, this paradigm offers improved translatability of self-administration findings to humans.
Certain groups are disproportionately affected by alcohol use disorder, namely those with depression. Utilizing the HomeBrew model, Mallory has studied the alcohol self-administration behavior of two closely related rat strains, selectively bred to encompass contrasting depression-like phenotypes. Her work thus far has demonstrated significantly enhanced alcohol consumption in rat models of endogenous depression vulnerability versus resistance and among adolescent female versus male groups, irrespective of depression susceptibility. These findings mirror current alcohol use trends in humans and underscore the impact of gender and comorbidities.
In its forthcoming stages, Mallory’s research will delve into the molecular determinants of the observed sex and strain differences in alcohol self-administration behavior. The SABA grant will support this effort by contributing to the cost of single-nuclei RNA sequencing–a technique capable of identifying gene expression differences with cell-type precision. The analysis will concentrate on the ventral hippocampus, a brain region strongly implicated in both depression and alcohol use disorder pathology. The co-segregation of alcohol consumption and depression-like traits captured within these inbred strains presents a rare opportunity to uncover genetic mechanisms relevant to both phenotypes. Moreover, since the genetic differences between the strains are minimal, the search for causal genes or variants can be streamlined. The main objective of her project is to elucidate specific biological processes and signaling pathways most relevant to alcohol consumption behavior, the primary cell type drivers, and potential sex-specific effects. This knowledge will offer invaluable insights for developing refined approaches to treating alcohol use disorder that address the distinct pathological foundations influenced by gender and comorbidity status.
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