Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice.

Area of Science:

• Genetics
• Neuroscience
• Animal Behavior

Background:

• The Drinking in the Dark (DID) model is a limited-access ethanol consumption paradigm in mice.
• High Drinking in the Dark (HDID) mice have been selectively bred for increased blood ethanol concentrations (BECs).
• Two replicate lines, HDID-1 (S27) and HDID-2 (S20), were developed from the same founder population.

Purpose of the Study:

• To characterize the genetic and behavioral traits of HDID-1 and HDID-2 mouse lines.
• To compare the selected lines with control HS mice.
• To analyze the response to selection for elevated BECs.

Main Methods:

• Selective breeding for 27 generations (HDID-1) and 20 generations (HDID-2) using the DID paradigm.
• Measurement of blood ethanol concentrations (BECs) and ethanol intake (g/kg) during DID tests.
• Assessment of withdrawal signs and ethanol elimination rates.

Main Results:

• Both HDID lines show a 4-5 fold increase in BECs compared to controls, with low heritability (h²=0.09).
• 80% of HDID-1 and 60% of HDID-2 mice achieve BECs >1.0 mg/ml.
• Ethanol intake increased by 60-80% in HDID lines; genetic influences were more significant than environmental ones for BEC and intake correlation.
• Drinking patterns showed concentration in the last 2 hours of the 4-hour session, with BECs peaking at 3-4 hours.
• HDID mice exhibit mild withdrawal signs hours after DID and do not differ in alcohol elimination rates.

Conclusions:

• Selective breeding effectively increased BECs in HDID mice, demonstrating the utility of the DID model for studying ethanol consumption.
• Genetic factors play a crucial role in the relationship between ethanol intake and BECs in these selected lines.
• HDID mice provide a valuable model for investigating the neurobiological underpinnings of high ethanol consumption and potential withdrawal symptoms.