Homer2 regulates alcohol and stress cross-sensitization

Area of Science:

• Neurobiology
• Addiction Science
• Behavioral Neuroscience

Background:

• Stress and alcohol use disorders (AUDs) are interconnected.
• Neurobiological mechanisms linking stress and AUDs require further elucidation.

Purpose of the Study:

• To investigate stress-induced cross-sensitization to alcohol's effects on behavior.
• To explore the role of nucleus accumbens (NAC) glutamate transmission in this interaction.

Main Methods:

• Unpredictable, chronic, mild stress (UCMS) procedure in mice.
• Behavioral assays for locomotor activity, alcohol intake, and intoxication.
• Immunoblotting to assess glutamate receptor-related proteins in NAC subregions.
• Analysis of Homer2 wild-type and knock-out mice.

Main Results:

• UCMS mice showed enhanced locomotor, intake, and intoxication responses to alcohol.
• UCMS altered levels of mGlu1α, GluN2b, and Homer2 in the NAC.
• Stress-alcohol locomotor cross-sensitization correlated with altered mGlu1α and ERK activity.
• Homer2 knock-out mice lacked stress-induced alcohol cross-sensitization.

Conclusions:

• Mild stress sensitizes animals to alcohol's psychomotor and rewarding effects.
• Neuroplasticity in NAC glutamate transmission may underlie stress-alcohol interactions in AUDs.