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

Area of Science:

• Neuroscience
• Addiction Research
• Genetics

Background:

• Mu-opioid receptors (MORs) in the amygdala and striatum are crucial for addictive and rewarding behaviors.
• Foxp2 is a marker for specific neuronal populations (intercalated cells and striatal medium spiny neurons) that express MORs and may influence alcohol consumption.

Purpose of the Study:

• To investigate the role of MORs in Foxp2-expressing neurons in alcohol consumption and related behaviors.
• To characterize the behavioral effects of deleting the MOR gene (Oprm1) in Foxp2-expressing neurons.

Main Methods:

• Generated mice with genetic deletion of MOR in Foxp2-expressing neurons (Foxp2-Cre/Oprm1fl/fl).
• Assessed alcohol consumption using an intermittent access (IA) task.
• Evaluated operant responding for sucrose reward, conditioned place aversion to morphine withdrawal, and locomotor activity.

Main Results:

• Deletion of MOR in Foxp2-expressing neurons increased sensitivity to quinine-adulterated ethanol.
• These mice consumed less alcohol during IA, responded less for sucrose, and showed reduced locomotor activity.
• The ability to learn reward tasks and develop morphine withdrawal aversion remained intact.

Conclusions:

• Foxp2-expressing neurons, by expressing MORs, are implicated in the escalation of alcohol intake.
• These findings suggest a role for Foxp2-MOR neurons in the development of compulsive-like alcohol drinking behaviors.