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Facilitated binge-like eating following chronic ethanol exposure in females
Thesis   Open access

Facilitated binge-like eating following chronic ethanol exposure in females

Samantha Marie Stine
Master of Science (M.S.), Drexel University
May 2022
DOI:
https://doi.org/10.17918/00001186
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Abstract

Alcoholism Compulsive eating Alcohol withdrawal syndrome
Individuals recovering from alcohol use disorder (AUD) are at elevated risk for developing binge eating behavior, potentially due to changes in reward circuitry. Women are being increasingly diagnosed with AUD and are more likely to develop eating disorders. We investigated if a history of chronic intermittent ethanol exposure (CIE) and withdrawal promoted subsequent binge eating in female mice to test the hypothesis that a history of CIE would increase binge-like eating behavior in female mice through alterations in the glutamatergic projections from the prefrontal cortex (PFC) to the nucleus accumbens (NAc). To model chronic exposure and withdrawal adult female C57BL/6J mice were exposed to a 4 week CIE paradigm by vapor inhalation or air control. After CIE, mice received limited home-cage access to highly palatable Chocolate Ensure Plus for 2 hrs/day Monday-Thursday for 6 weeks. Differences between groups were tested by mixed model ANOVA (with access days as the within-subjects factor). CIE and binge-eating induced alterations in the glutamate system were assessed using qPCR analysis of glutamate transporters vGLUT1 and vGLUT2 of the mPFC tissue samples microdissected. To test the role of PFC projections to the NAc in regulating binge-like eating, a separate cohort of mice received a microinjection of an AAV expressing a GiDREADD in the PFC. The DREADD ligand CNO was administered in the NAc to selectively silence PFC NAc projections. Differences between groups were tested by mixed ANOVA (CNO vs saline as the within subjects factor), with post-hoc tests where appropriate. Our findings indicated that CIE-exposed mice increased binge-like eating compared to control at the initiation of the binge paradigm, as indicated by greater Ensure intake (kcal/body weight) and a greater percentage of daily caloric intake from Ensure. These behavioral changes were accompanied by reduced vGLUT1 and vGLUT2 mRNA expression in the PFC of CIE mice compared to Air controls. Consistent with changes in PFC glutamate signaling, chemogenetic silencing of discrete glutamatergic PFC projections to the NAc increased binge-like eating. Importantly, this model met criteria for binge-like eating and identified chronic ethanol induced changes in binge-like eating and PFC glutamate system. This suggests that women may exhibit an increased vulnerability to acquisition of binge eating behavior following withdrawal from alcohol use. Further, modulation of the glutamate system to reduce binge-like eating during ethanol withdrawal may represent a feasible therapeutic target.

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