Loss of RAB-3/A in Caenorhabditis elegans and the mouse affects behavioral response to ethanol.
The mechanisms by which ethanol induces changes in behavior are not well understood. Here, we show that Caenorhabditis elegans loss-of-function mutations in the synaptic vesicle-associated RAB-3 protein and its guanosine triphosphate exchange factor AEX-3 confer resistance to the acute locomotor effects of ethanol. Similarly, mice lacking one or both copies of Rab3A are resistant to the ataxic and sedative effects of ethanol, and Rab3A haploinsufficiency increases voluntary ethanol consumption. These data suggest a conserved role of RAB-3-/RAB3A-regulated neurotransmitter release in ethanol-related behaviors.
Kapfhamer
D
D
The Ernest Gallo Clinic and Research Center, University of California at San Francisco, Emeryville, CA 94608, USA.
Bettinger
J C
JC
Davies
A G
AG
Eastman
C L
CL
Smail
E A
EA
Heberlein
U
U
McIntire
S L
SL
D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020268:Alcohol-Induced Disorders, Nervous System / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003244:Consciousness Disorders / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology; D006239:Haplotypes / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020692:rab3 GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020826:rab3A GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002492:Central Nervous System Depressants; D000431:Ethanol; D020692:rab3 GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein