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Mu-opioid receptor knockout on Foxp2-expressing neurons reduces aversion-resistant alcohol drinking
Harrison M Carvour1, Charlotte A E G Roemer1, D'Erick P Underwood1
1Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA.
Pharmacology, Biochemistry, and Behavior
|December 8, 2024
Summary
Deleting mu-opioid receptors (MORs) in Foxp2-expressing neurons reduced alcohol consumption and increased sensitivity to alcohol aversion. These findings suggest Foxp2-expressing neurons are involved in compulsive alcohol drinking.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Mu-opioid receptors (MORs) in the amygdala and striatum are crucial for reward and addiction.
- Foxp2 is a marker for specific neuronal populations (intercalated cells and striatal medium spiny neurons) expressing MORs, relevant to alcohol consumption.
Purpose of the Study:
- To investigate the role of MORs in Foxp2-expressing neurons in alcohol-related behaviors.
- To characterize the behavioral effects of deleting the MOR gene (Oprm1) in Foxp2-expressing neurons.
Main Methods:
- Generated Foxp2-Cre/Oprm1fl/fl mice (male and female) with MOR deletion in Foxp2-expressing neurons.
- Assessed aversion-resistant alcohol consumption (intermittent access task), sucrose reward seeking (operant responding), morphine withdrawal aversion (CPA), and locomotor activity.
Main Results:
- MOR deletion in Foxp2-expressing neurons increased sensitivity to quinine-adulterated alcohol.
- Mice with MOR deletion consumed less alcohol and showed reduced baseline and morphine-induced activity.
- A trend towards reduced sucrose seeking was observed; learning and aversion to morphine withdrawal were unaffected.
Conclusions:
- Foxp2-expressing neurons play a significant role in the escalation of alcohol intake.
- Deletion of MORs in these neurons may reduce compulsive-like alcohol drinking behaviors.
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