Author Date

2024-11-20

Degree Name

BS

Department

Neuroscience

College

Life Sciences

Publication Date

2025-12-31

First Faculty Advisor

Jordan T. Yorgason

First Faculty Reader

Michael Brown

Honors Coordinator

Rebekka Matheson

Keywords

Fatty foods, Ethanol, Nucleus Accumbens, Bile Acids, Cholinergic Interneurons, Dopamine

Abstract

Fatty foods and ethanol increase hepatic bile acid (BA) secretion and have strong reinforcing effects, implicating changes in mesolimbic circuitry. Previous studies have shown that high-fat diets alter striatal dopamine (DA) receptor expression, and that brain slices that are directly exposed to ethanol in vitro display concentration-dependent alterations in cholinergic interneuron (CIN) firing rates in the nucleus accumbens (NAc). However, few studies have adopted a whole-body approach and investigated the potential role of peripheral organs in contributing to fatty food or ethanol effects on mesolimbic circuitry. The current study tested BA effects in the NAc to discern whether BAs have the potential to act as hepatic signaling molecules influencing mesolimbic activity following ethanol or fatty food consumption. Using cell-attached physiology recordings to measure CIN firing rates, we found that lower BA concentrations (1-10 μM) increase CIN firing rates and that higher BA concentrations (1-10 mM) decrease CIN firing rates. We also found that BA effects on accumbal CINs are mediated by the Takeda G Protein-Coupled Receptor 5 (TGR5). Moreover, ethanol-treated liver tissue reduces accumbal CIN firing rates, similar to BA conditions, suggesting comparable mechanisms for influencing CIN firing. However, voltammetry measures of BA-induced DA decreases, which recapitulated BA effects on CIN firing, did not exhibit a similar reduction from ethanol-treated liver tissue. Taken together, these results provide new insights into BA potential to influence reward-related neural circuitry.

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Available for download on Wednesday, June 30, 2027

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