Alcohol use disorder (AUD) is an issue facing many Americans, and many neural mechanisms can lead to the development of this disorder. The present study aimed to characterize the development of AUD behaviors using a new transgenic line of mice with their mu-opioid receptors (MORs) genetically deleted on intercalated (ITC) cells. MORs are the most common opioid receptors in the endogenous opioid system. Animal studies involving the pharmacological blockade of these receptors in the amygdala have demonstrated reduced alcohol-seeking behaviors. ITC cells are clusters of GABAergic interneurons that mediate activity in the amygdala via inhibitory control. Previous studies have demonstrated that ethanol can induce GABA release from ITC terminals, suggesting that these cells may have a role in alcohol-related behaviors. ITC cells are the only amygdala neurons expressing the FoxP2 gene. Since these mice are modified to be missing MORs on FoxP2-expressing neurons, ITC cells are the only neurons that are missing these receptors in the amygdala. To characterize the development of AUD behaviors in these mice, we ran a 24-hour, two-bottle choice intermittent access (IA) drinking experiment using 44 subjects equally balanced for experimental (MOR-knockout) and control (wild-type) groups and sex. Mice self-administered water or 20% ethanol every other day (Mon-Wed-Fri) for five weeks and received just water on intervening days and weekends. During the fifth week, the bitter tastant quinine was added to the ethanol in escalating concentrations (10, 100, and 200 mg/L) to test their aversion-resistance (drinking despite negative consequences). Bottles were weighed before and after each drinking session to measure consumption. Results from this study indicate no significant differences in ethanol consumption between the two mouse groups during the first four weeks. However, the MOR-knockout mice preferred ethanol with 100 and 200 mg/L quinine concentrations significantly less from baseline. At the same time, the wild-type group only had a significant decrease in ethanol preference at the 200 mg/L quinine concentration. Sex differences were found in this study, with wild-type and MOR-knockout females drinking significantly more ethanol than their male counterparts. These results suggest that mice with MOR-targeted deletion of FoxP2 expression neurons demonstrate less aversion-resistant drinking, and MOR expression on ITC cells may contribute to the development of this behavior.
Author(s): Harrison Carvour, Psychology Major
Advisor(s): Anna Radke, Department of Psychology
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