Mu-opioid receptors (MORs) in the amygdala and striatum are important in addictive and rewarding behaviors. For the current series of studies, we characterized the behavior of mice with genetic deletion of the MOR gene Oprm1 in FoxP2-expressing neurons (FoxP2-Cre/Oprm1fl/fl). FoxP2 is expressed in intercalated cells of the amygdala and a subset of striatal medium spiny neurons, both of which express MORs in wild-type mice. FoxP2-Cre/Oprm1fl/fl mice were tested for aversion-resistant alcohol consumption using an intermittent access (IA) task, conditioned place aversion (CPA) to morphine withdrawal, and operant responding for a sucrose reward. For IA, mice received the choice of 20% ethanol and water for 24 hours three days a week, with mice receiving only water on intervening days for five weeks. In the fifth week, escalating quinine concentrations at 10, 100, and 200 mg/L were added to the ethanol solution. Results from this study indicated that mice with the MOR-knockout were more sensitive to the quinine in ethanol and less aversion-resistant, as they decreased ethanol consumption from baseline at all quinine concentrations, while control animals did not. For the CPA study, mice received four conditioning days: two with morphine/naloxone injections and two with saline/saline, with 30 minutes between each injection. Following the second injection, mice were confined to one side of the conditioning apparatus. Both wild-type and knockout mice demonstrated withdrawal-induced aversion. For operant conditioning, mice were trained to nosepoke for 10% sucrose before undergoing a fading procedure with decreasing concentrations of 10%, 5%, and 2% on a fixed ratio (FR) 1 schedule. Lastly, mice were tested for aversion-resistance with escalating quinine concentrations of 10, 100, and 200 mg/L in the sucrose on an FR3 schedule. Results from this study showed that mice with FoxP2 MOR deletion did not affect sucrose responding, but did lead to decreased responding on an FR3 schedule. Together, these results suggest that MOR expression on FoxP2-expressing neurons is not necessary for alcohol consumption or expression of opioid withdrawal but may be involved in aversion-resistant reward seeking.
Author(s): Harrison M. Carvour, Megan Robertson, Natella Parsadanyan, Mallory Miller, D’Erick P. Underwood, Charlotte A.E.G. Roemer, Ezra P. Eccles, Thomas W. Perry, Kiara D. Ream, Anna K. Radke, Ph.D.
Advisor(s): Anna Radke, Department of Psychology
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