CLASSICAL GENETIC-ANALYSIS OF NICOTINE-INDUCED SEIZURES AND NICOTINIC RECEPTORS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (3) , 545-554
Abstract
C3H/2lbg mice are more sensitive to nicotine-induced seizure than are DBA/2lbg mice. There are also differences in .alpha.-bungarotoxin (.alpha.-BTX) binding in the hippocampus and midbrain of these 2 strains, with the C3H mice having greater binding. Because .alpha.-BTX and nicotine appear to bind to nicotinic receptors in the CNS, 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 .times. C3H and F1 .times. DBA) generations from these 2 strains was utilized. Dose-response curve for nicotine-induced seizures were constructed for both parental strains and all crosses derived from them. Nicotinic receptors were also measured in 3 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 6 generations for .alpha.-BTX binding in the hippocampus paralleled that for seizure sensitivty. 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.

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