Mu-opioid receptor knockout on Foxp2-expressing neurons reduces aversion-resistant alcohol drinking.

Autor: Carvour HM; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Roemer CAEG; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Underwood DP; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Padilla ES; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Sandoval O; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Robertson M; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Miller M; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Parsadanyan N; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Perry TW; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA., Radke AK; Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA. Electronic address: aradke@miamioh.edu.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2024 Dec 06; Vol. 247, pp. 173932. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1016/j.pbb.2024.173932
Abstrakt: Mu-opioid receptors (MORs) in the amygdala and striatum are important in addictive and rewarding behaviors. The transcription factor Foxp2 is a genetic marker of intercalated (ITC) cells in the amygdala and a subset of striatal medium spiny neurons (MSNs), both of which express MORs in wild-type mice and are neuronal subpopulations of potential relevance to alcohol-drinking 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/Oprm1 fl/fl ). Male and female Foxp2-Cre/Oprm1 fl/fl mice were generated and heterozygous Cre+ (knockout) and homozygous Cre- (control) animals were tested for aversion-resistant alcohol consumption using an intermittent access (IA) task, operant responding for a sucrose reward, conditioned place aversion (CPA) to morphine withdrawal, and locomotor sensitization to morphine. The results demonstrate that deletion of MOR on Foxp2-expressing neurons renders mice more sensitive to quinine-adulterated alcohol. Mice with the deletion (vs. Cre- controls) also consumed less alcohol during the final sessions of the IA task, were less active at baseline and following morphine injection, and there was a trend toward less responding for sucrose under an FR3 schedule. Foxp2-MOR deletion did not impair the ability to learn to respond for reward or develop a conditioned aversion to morphine withdrawal. Together, these investigations demonstrate that Foxp2-expressing neurons may be involved in escalation of alcohol consumption and the development of compulsive-like alcohol drinking.
Competing Interests: Declaration of competing interest The authors declare no conflicting interests in this work.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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