SENSITIVITY TO THE SEIZURE-INDUCING EFFECTS OF NICOTINE IS ASSOCIATEDWITH STRAIN-SPECIFIC VARIANTS OF THE ALPHA-5 AND ALPHA-7 NICOTINIC RECEPTOR SUBUNIT GENES

Restriction fragment length polymorphisms (rflps) have been identified for the nicotinic ACh receptor subunit genes alpha 5 and alpha 7 betw een two mouse strains (C3H/2ibg and DBA/2ibg) that differ in Sensitivi ty to the convulsant effects of nicotine. In the study reported here, F2 animals derived from these two parental stains were tested for thei r sensitivity to the convulsant effects of nicotine as measured by sei zure frequency and overall sensitivity score. Subsequently, the animal s were genotyped for the alpha 5 and alpha 7 rflps. In addition, level s of alpha-bungarotoxin (alpha-BTX) binding were measured in four brai n regions (colliculi, hippocampus, hypothalamus and striatum) to deter mine whether there is a correlation among alpha-BTX binding levels, se nsitivity to nicotine and nicotinic ACh receptor subunit genotype. A s ignificant relationship was observed between alpha 5 and alpha 7 genot ype and sensitivity to nicotine. In addition, the alpha 7 rflp signifi cantly correlated with levels of alpha-BTX binding in hippocampus, col liculi and striatum. The alpha 5 rflp did not correlate with alpha-BTX binding levels in any brain region. Levels of alpha-BTX binding did n ot correlate with nicotine-induced seizure sensitivity or overall nico tine sensitivity score in any of the four brain regions examined.