Sensitivity to the seizure-inducing effects of nicotine is associated with 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 between two mouse strains (C3H/2ibg and DBA/2ibg) that differ in sensitivity to the convulsant effects of nicotine. In the study reported here, F2 animals derived from these two parental stains were tested for their sensitivity to the convulsant effects of nicotine as measured by seizure frequency and overall sensitivity score. Subsequently, the animals were genotyped for the alpha 5 and alpha 7 rflps. In addition, levels of alpha-bungarotoxin (alpha-BTX) binding were measured in four brain regions (colliculi, hippocampus, hypothalamus and striatum) to determine whether there is a correlation among alpha-BTX binding levels, sensitivity to nicotine and nicotinic ACh receptor subunit genotype. A significant relationship was observed between alpha 5 and alpha 7 genotype and sensitivity to nicotine. In addition, the alpha 7 rflp significantly correlated with levels of alpha-BTX binding in hippocampus, colliculi and striatum. The alpha 5 rflp did not correlate with alpha-BTX binding levels in any brain region. Levels of alpha-BTX binding did not correlate with nicotine-induced seizure sensitivity or overall nicotine sensitivity score in any of the four brain regions examined.
Stitzel
J A
JA
Institute for Behavioral Genetics, University of Colorado, Boulder, USA.
Blanchette
J M
JM
Collins
A C
AC
D000818:Animals; D001921:Brain / Q000378:metabolism; D002038:Bungarotoxins / Q000378:metabolism; D005838:Genotype; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D009538:Nicotine / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012640:Seizures / Q000139:chemically induced*; D013045:Species Specificity
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D009538:Nicotine