Reduced ethanol consumption and preference in cocaine- and amphetamine-regulated transcript (CART) knockout mice

Area of Science:

• Neuroscience
• Addiction Research
• Molecular Biology

Background:

• Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide linked to drug addiction.
• Research on CART's role in alcohol use disorders, including alcoholism, is limited.
• CART's involvement in psychostimulant addiction is well-documented.

Purpose of the Study:

• To investigate the role of CART in ethanol appetitive behaviors using a CART knockout (KO) mouse model.
• To compare ethanol consumption and preference between CART wild type (WT) and KO mice.
• To assess the impact of CART deficiency on taste perception, ethanol metabolism, and sensitivity.

Main Methods:

• A two-bottle choice, unlimited-access paradigm comparing ethanol (3%-21%) and water consumption in WT and KO mice.
• Measurement of quinine (bitter) and saccharin (sweet) solution consumption to assess taste perception.
• Comparison of ethanol metabolism rates and ethanol sensitivity between genotypes.

Main Results:

• CART KO mice exhibited significantly lower ethanol consumption and preference compared to WT mice across both sexes.
• These behavioral differences were not attributable to variations in bitter/sweet taste perception or ethanol metabolism.
• While male mice showed no difference in ethanol sensitivity, CART KO females displayed heightened sensitivity.

Conclusions:

• CART plays a significant role in regulating ethanol appetitive behaviors.
• CART deficiency reduces alcohol preference and may influence ethanol sensitivity, particularly in females.
• CART represents a potential therapeutic target for alcoholism treatment and enhancing abstinence.