Variability in response to nicotine in the LSxSS RI strains:: potential role of polymorphisms in α4 and α6 nicotinic receptor genes

Several studies have shown that genetic factors influence the effects of nicotine on respiration, acoustic startle, Y-maze crosses and rears, heart rate and body temperature in the mouse. Recently, we identified restriction fragment length polymorphisms (RFLPs) associated with the alpha(4) (Chrna4) and alpha(6) (Chrna6) nicotinic cholinergic receptor genes in the recombinant inbred (RI) strains derived from the Long-Sleep (LS) and Short-Sleep (SS) mouse lines. The alpha(4) polymorphism has been identified as a point-mutation at position 529 (threonine to alanine) and the a6 polymorphism has not yet been identified. The studies on Y-maze crosses than those strains carrying the SS-like alpha(6) RFLP. These results suggest that genetically determined differences in sensitivity to nicotine may be explained, in part, by variability associated with at least two of the neuronal nicotinic receptor genes, alpha(4) and alpha(6)-Pharmacogenetics 12:197-208 (C) 2002 Lippincott Williams Wilkins.