GABA(B) receptor agonist only reduces ethanol drinking in light-drinking mice

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Baclofen, a GABA(B) receptor agonist, has shown mixed results in reducing ethanol consumption.
• Previous research indicated differences in GABA(B1) and GABA(B2) subunit transcription in mice with "loss of control" over ethanol intake.

Purpose of the Study:

• To investigate the effect of baclofen on ethanol intake in mice with distinct drinking behaviors using a free-choice paradigm.
• To explore the role of GABA(B) receptor subunit balance in baclofen's efficacy.

Main Methods:

• Adult male Swiss mice were categorized into "loss of control" (A), heavy (H), and light (L) drinkers based on ethanol preference and intake.
• Mice received intraperitoneal injections of baclofen (1.25, 2.5, or 5.0 mg/kg) or saline across different experimental phases (acquisition, withdrawal, reexposure, adulteration).
• Ethanol intake was measured 24 hours after injections in a free-choice setting with ethanol and water.

Main Results:

• Baclofen significantly reduced ethanol intake in light (L) drinkers.
• Heavy (H) drinkers showed a reduction in ethanol intake compared to the acquisition phase after baclofen treatment.
• Mice with "loss of control" (A) maintained high ethanol intake despite baclofen administration.

Conclusions:

• Baclofen's efficacy in reducing ethanol intake is dependent on the individual's drinking profile.
• Disproportionate transcription levels of GABA(B1) and GABA(B2) subunits may explain the lack of response to baclofen in mice with "loss of control".
• These findings underscore the need to consider individual differences in ethanol consumption patterns when evaluating baclofen as a potential treatment for alcohol use disorder.