Alcohol-related genes: contributions from studies with genetically engineered mice

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Since 1996, numerous genes have been investigated for their role in ethanol's effects in mice.
• Studies primarily focus on genes within the brain, affecting neurotransmitter systems, neurohormones, and signaling molecules.

Purpose of the Study:

• To review published reports on the effects of gene modifications on ethanol responses in mice.
• To synthesize findings on how genetic alterations influence ethanol self-administration, reward, sedation, and neuroadaptation.

Main Methods:

• Review of 141 published reports examining the impact of 93 genes on ethanol responses.
• Analysis of genetic modifications including gene deletion, overexpression, and knock-in in mice.
• Examination of various ethanol-related behaviors such as self-administration, sedation, and neuroadaptation.

Main Results:

• Approximately 25% of engineered mutations increased ethanol self-administration, 33% decreased it, and 40% had no significant effect.
• Observed effects on self-administration were often modest and procedure-dependent.
• Findings reinforce the roles of serotonin, GABA, opioids, and dopamine in alcohol research, and suggest novel roles for protein kinase C and GIRK channels.

Conclusions:

• Genetic studies in mice provide valuable insights into the complex mechanisms underlying ethanol's effects.
• The review highlights established and novel neurobiological systems involved in alcohol's influence.
• Emerging research on cannabinoid systems shows promise for future clinical applications in alcohol use disorder.