Loss of RAB-3/A in Caenorhabditis elegans and the mouse affects behavioral response to ethanol.

August 1, 2008

Kapfhamer D, Bettinger JC, Davies AG, Eastman CL, Smail EA, Heberlein U, McIntire SL.
2008 Genes Brain Behav. 7(6):669-76. doi: 10.1111/j.1601-183X.2008.00404.x. PMCID: PMC3526002

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.