Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans

Andrew G Davies; Jill C Bettinger; Tod R Thiele; Meredith E Judy; Steven L McIntire

doi:10.1016/j.neuron.2004.05.004

Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans

Neuron. 2004 Jun 10;42(5):731-43. doi: 10.1016/j.neuron.2004.05.004.

Authors

Andrew G Davies¹, Jill C Bettinger, Tod R Thiele, Meredith E Judy, Steven L McIntire

Affiliation

¹ Ernest Gallo Clinic and Research Center, Department of Neurology, Programs in Neuroscience and Biomedical Science, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA.

PMID: 15182714
DOI: 10.1016/j.neuron.2004.05.004

Abstract

Variation in the acute response to ethanol between individuals has a significant impact on determining susceptibility to alcoholism. The degree to which genetics contributes to this variation is of great interest. Here we show that allelic variation that alters the functional level of NPR-1, a neuropeptide Y (NPY) receptor-like protein, can account for natural variation in the acute response to ethanol in wild strains of Caenorhabditis elegans. NPR-1 negatively regulates the development of acute tolerance to ethanol, a neuroadaptive process that compensates for effects of ethanol. Furthermore, dynamic changes in the NPR-1 pathway provide a mechanism for ethanol tolerance in C. elegans. This suggests an explanation for the conserved function of NPY-related pathways in ethanol responses across diverse species. Moreover, these data indicate that genetic variation in the level of NPR-1 function determines much of the phenotypic variation in adaptive behavioral responses to ethanol that are observed in natural populations.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Animals, Genetically Modified
Behavior, Animal / drug effects*
Caenorhabditis elegans / drug effects*
Caenorhabditis elegans / genetics
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / physiology*
Central Nervous System Depressants / metabolism
Central Nervous System Depressants / pharmacology*
Chromosome Mapping / methods
Dose-Response Relationship, Drug
Drug Tolerance / genetics
Ethanol / metabolism
Ethanol / pharmacology*
Genetic Variation / drug effects*
Genetic Variation / genetics
Green Fluorescent Proteins
Luminescent Proteins / metabolism
Models, Biological
Mutation
RNA, Messenger / biosynthesis
Receptors, Neuropeptide Y / genetics
Receptors, Neuropeptide Y / physiology*
Reverse Transcriptase Polymerase Chain Reaction / methods
Social Behavior
Species Specificity
Substance Withdrawal Syndrome / physiopathology
Time Factors
Transformation, Genetic

Substances

Caenorhabditis elegans Proteins
Central Nervous System Depressants
Luminescent Proteins
NPR-1 protein, C elegans
RNA, Messenger
Receptors, Neuropeptide Y
Green Fluorescent Proteins
Ethanol