Classical genetic analysis of nicotine-induced seizures and nicotinic receptors

C3H/2lbg mice are more sensitive to nicotine-induced seizures than are DBA/2lbg mice. There are also differences in alpha-bungarotoxin (alpha-BTX) binding in the hippocampus and midbrain of these two strains, with the C3H mice having greater binding. Because alpha-BTX and nicotine appear to bind to nicotinic receptors in the central nervous system, it is possible that there may be a relationship between seizure sensitivity after a nicotine dose and nicotinic receptor concentration. To examine this relationship, a classical cross producing F1, F2 and backcross (F1 X C3H and F1 X DBA) generations from these two strains was utilized. Dose-response curves for nicotine-induced seizures were constructed for both parental strains and all crosses derived from them. Nicotinic receptors were also measured in three brain regions: cortex, midbrain and hippocampus. Both DL-[3H]nicotine and alpha-[125I]BTX were used to measure nicotinic receptors. The pattern of results for the six generations for alpha-BTX binding in the hippocampus paralleled that for seizure sensitivity. These results suggest that strain differences for both seizure sensitivity and receptor concentration in the hippocampus may be due to allelic differences at a single autosomal locus, with dominance for low seizure susceptibility and fewer alpha-BTX receptors.