Psychology Ph.D. Dissertations

Using Fecal Microbial Transfer to Alter Drinking Behavior in a Rat Model of Alcoholism and Correlations with Dopamine Receptor Expression

Date of Award

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Psychology

First Advisor

Howard Casey Cromwell (Committee Chair)

Second Advisor

Verner Bingman (Committee Member)

Third Advisor

Sherri Horner (Other)

Fourth Advisor

Michael Zickar (Committee Member)

Fifth Advisor

Daniel Weigmann (Committee Member)

Abstract

Addiction disorders, majorly governed by the mesolimbic dopamine system, constitute a global health crisis, with alcoholism being particularly prevalent and pernicious. Alterations of the gut microbiome correlate with alterations in addiction pathologies, both physiological and behavioral. Fecal Microbial Transfer is an established research and clinical technique for manipulating the Brain-Gut-Microbiome Axis in many conditions. Ethanol is known to have massive impacts on both the gut and dopamine systems, potentially producing impacts on the latter via some action on the former. The Alcohol Preferring and Non-Preferring rat models are well suited for investigating neuropsychological processes related to alcohol addiction. We performed FMT between P and NP rats during chronic ethanol exposure to investigate the effect on drinking behaviors, and then we examined the expression of dopamine receptors 1 (D1R) and 2 (D2R) in three brain regions related to addiction (hippocampus, prefrontal cortex, and nucleus accumbens). We found that NP rats drank and preferred alcohol significantly less than P rats before, during, and after the FMT treatment during chronic ethanol exposure. Differences in drinking behaviors were not statistically significant between weeks, though there were slight patterns of a bi-directional influence, with P rats decreasing and NP rats increasing drinking during FMT. Levels of the two receptor types correlated positively with each other in each brain region. D1R in hippocampus and nucleus accumbens correlated positively with preference for the weaker concentration of ethanol, and both D1R and D2R correlated positively with intake of the stronger concentration after the FMT treatment. We also found that in P rats, FMT reduced alpha diversity of the gut microbiome, and reduced abundance of Akkermancia municiphila, and Bifidobacterium animalis; these gut conditions are associated with healthier outcomes, which may suggest that FMT impacted drinking behavior through the protective effects of these beneficial microbes, thereby decreasing the need for them over time. Our findings suggest that P and NP rats have distinct gut microbiome as well as neurobehavioral phenotypes, that the two interact systemically, and that functional features of these phenotypes can be transferred bi-directionally via FMT, providing support for the use of FMT as an innovative clinical approach to addiction and mental illness.

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