Genetic Variation in Alcohol Tolerance

Abstract

STKE The nematode Caenorhabditis elegans exhibits a decline in locomotor activity as an acute response to ethanol. In the continued presence of ethanol, the strains N2 and CB4856 show slow and rapid recovery (albeit incomplete) of movement, respectively. Through genetic analysis, Davies et al. map the differences in this rate of adaptation to ethanol to npr-1 , a gene that encodes a homolog to the mammalian neuropeptide Y (NPY) receptor. The CB4856 allele of npr-1 is lower-functioning than that of N2, and the authors propose that NPR-1 exerts an inhibitory influence on the development of tolerance. Interestingly, these alleles of npr-1 are known to account for differences in behavior (N2 are solitary, while CB4856 are more sociable), yet the social behavior roles of NPR-1 and the ethanol tolerance effect were separable based on genetic interactions and targeted expression studies. NPY signaling has been implicated in alcohol responsiveness in mammals, and further investigation with the genetically tractable nematode may lead to additional insight into the molecular mechanisms that contribute to alcoholism. — NG Neuron 42 , 731 (2004).