Midazolam, methamphetamine, morphine and nicotine intake in high-drinking-in-the-dark mice

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• The high-drinking-in-the-dark (HDID) mouse lines were selectively bred for high voluntary alcohol consumption in the drinking-in-the-dark (DID) task, serving as a genetic risk model for binge-like alcohol intake.
• Limited information exists regarding the HDID lines' consumption patterns of other addictive drugs.

Purpose of the Study:

• To investigate the voluntary consumption of midazolam, methamphetamine, morphine, and nicotine by HDID-1 and HDID-2 mouse lines in a DID test.
• To compare the drug consumption levels of HDID lines with their founders, heterogeneous stock/Northport (HS/NPT) mice, at tested concentrations.

Main Methods:

• HDID-1, HDID-2, and HS/NPT mice were given four days of access to each of the four drugs using a single-bottle, limited-access DID paradigm.
• Consumption levels of methamphetamine (40 µg/ml), midazolam (150 µg/ml), morphine (700 µg/ml), and nicotine were measured in male and female mice.

Main Results:

• Both HDID lines voluntarily consumed all four tested drugs (midazolam, methamphetamine, morphine, nicotine).
• Significant differences in intake were observed for nicotine, midazolam, and morphine, but not methamphetamine.
• Both HDID lines consumed significantly more midazolam than HS/NPT mice, suggesting a shared genetic basis for binge ethanol and midazolam intake.
• HDID-2 mice, but not HDID-1 mice, consumed significantly more morphine and nicotine than HS/NPT mice.

Conclusions:

• HDID mouse lines are suitable models for studying voluntary consumption of various drugs beyond ethanol.
• These findings highlight potential genetic differences between HDID lines concerning their susceptibility to elevated drug intake.
• The results support a shared genetic vulnerability for binge intake of both ethanol and midazolam.