Transgenic over expression of nicotinic receptor alpha 5, alpha 3, and beta 4 subunit genes reduces ethanol intake in mice

Abuse of alcohol and smoking are extensively co-morbid. Some studies suggest partial commonality of action of alcohol and nicotine mediated through nicotinic acetylcholine receptors (nAChRs). We tested mice with transgenic over expression of the alpha 5, alpha 3, beta 4 receptor subunit genes, which lie in a cluster on human chromosome 15, that were previously shown to have increased nicotine self-administration, for several responses to ethanol. Transgenic and wild-type mice did not differ in sensitivity to several acute behavioral responses to ethanol. However, transgenic mice drank less ethanol than wild-type in a two-bottle (ethanol vs. water) preference test. These results suggest a complex role for this receptor subunit gene cluster in the modulation of ethanol's as well as nicotine's effects. JCC was supported by the US Department of Veterans, by NIH grants AA10760 and AA13519, and by a grant to MD from the DURSI. This work was funded by the Catalan Government (2009SGR1313) Spanish Ministry of Education and SciencesSAF2007-60827, SAF2007-31093-E, SAF2010-16427, Phecomp (EU LSHM-CT-2007-037669, EU/FIS PS09102673), Fundación Ramón Areces, Reina Sofia, Marató TV3, and CIBERER. OV and JRM were supported by the Spanish Ministry of Health (RTA001/06/1001-FEDER), Spanish Ministry of Education and Sciences SAF 2010-15793, and the Generalitat de Catalunya (2009 SGR 684). We thank Alex Bachmanov for sharing unpublished data.