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Alcohol Drinking in MCH Receptor-1-Deficient Mice


  • This research was supported by NIH Grant DK17844 and NIAAA Grant F31 AA015819.

Reprint requests: Elizabeth A. Duncan, National Institute of Drug Abuse, 5500 Nathan Shock Dr Baltimore, MD 21224; E-mail:


Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance of this finding is unclear, we tested the hypothesis that endogenous MCH signaling enhances alcohol consumption.

Methods: Alcohol intake was assessed in male and female wildtype (WT), heterozygous (HET), and homozygous MCH receptor-1-deficient (KO) mice. Mice were given 24-hour access to a series of alcohol-containing solutions. Following this, the mice were given limited (1-hour) access to 10% alcohol. Finally, mice were allowed 24-hour access to sucrose/quinine as a caloric control and a means to assess taste preference. A naïve cohort of male WT and KO mice was tested for alcohol clearance following intraperitoneal administration of 3 g/kg alcohol. Another naïve cohort of female mice was utilized to confirm that intracerebroventricular administration of MCH (5 μg) would augment alcohol drinking in mice.

Results: Exogenous MCH enhanced 10% alcohol consumption in mice (saline=0.45±0.08 g/kg, 5 μg MCH=0.94±0.20 g/kg). Male KO mice consumed more 10% alcohol (11.50±1.31 g/kg) than WT (6.26±1.23 g/kg) and HET mice (6.49±1.23 g/kg) during ad libitum access. However, alcohol intake was similar among genotypes during 1 hour daily access. Male KO mice tended to consume less 17.75% sucrose+1.3 mM quinine than controls (WT=10.5±3.6, HET=7.5±1.7, KO=4.4±0.9 g/kg). Alcohol metabolism was similar between WT and KO mice.

Conclusions: The finding that male KO consume more alcohol than WT and HET mice, are reminiscent of the counterintuitive reports that KO mice are hyperphagic and yet eat more when administered exogenous MCH. Changes in taste preference or alcohol metabolism do not appear to be important for the increased alcohol drinking in KO mice.