Ethanol drinking in withdrawal seizure-prone and -resistant selected mouse lines

Area of Science:

• Neuroscience
• Genetics
• Behavioral Science

Background:

• Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice were selectively bred for severe or mild ethanol withdrawal convulsions.
• Previous studies suggested an inverse correlation between ethanol consumption and withdrawal severity, but with limitations.

Purpose of the Study:

• To thoroughly assess ethanol preference and binge-drinking behaviors in WSP and WSR mouse lines.
• To investigate the genetic correlation between ethanol consumption and withdrawal severity.
• To determine if two-bottle preference and Drinking in the Dark (DID) are genetically distinct traits.

Main Methods:

• Bidirectional selective breeding of WSP and WSR mouse lines based on ethanol withdrawal severity.
• Two-bottle ethanol preference tests in both sexes across replicate lines.
• Sucrose, saccharin, and quinine preference tests in naive mice.
• Drinking in the Dark (DID) test for binge-like ethanol consumption.
• Assessment of handling-induced convulsions (HICs) after acute withdrawal following DID.

Main Results:

• WSR-2 female mice showed greater ethanol preference than WSP-2, confirming prior findings.
• WSP-1 mice exhibited higher ethanol consumption than WSR-1 mice, indicating line-specific differences.
• WSP mice consumed more ethanol during DID and achieved higher blood ethanol concentrations than WSR mice.
• Acute withdrawal after DID revealed mild, significant HICs in WSP mice.

Conclusions:

• Ethanol preference and binge drinking (DID) appear to be genetically distinguishable traits.
• The genetic correlation between ethanol consumption and withdrawal severity is complex and may vary between selected lines.
• Further research is warranted to elucidate the genetic underpinnings of these distinct ethanol-related behaviors.