Abstract
Restriction fragment length polymorphisms (rflps) have been identified for the nicotinic ACh receptor subunit genes α5 and α7 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 α5 and α7 rflps. In addition, levels of α-bungarotoxin (α-BTX) binding were measured in four brain regions (colliculi, hippocampus, hypothalamus and striatum) to determine whether there is a correlation among α-BTX binding levels, sensitivity to nicotine and nicotinic ACh receptor subunit genotype. A significant relationship was observed between α5 and α7 genotype and sensitivity to nicotine. In addition, the α7 rflp significantly correlated with levels of α-BTX binding in hippocampus, colliculi and striatum. The α5 rflp did not correlate with α-BTX binding levels in any brain region. Levels of α-BTX binding did not correlate with nicotine-induced seizure sensitivity or overall nicotine sensitivity score in any of the four brain regions examined.
Footnotes
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Send reprint requests to: Jerry A. Stitzel, Institute for Behavioral Genetics, University of Colorado Campus Box 447, Boulder, CO 80309.
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↵1 This work was supported by grants DA-03194 and DA-10156 from the National Institute on Drug Abuse. A.C.C. is supported in part by a Research Scientist Award (DA-00197).
- Abbreviations:
- α-BTX
- α-bungarotoxin
- ANOVA
- analysis of variance
- KRH
- Krebs-Ringer’s HEPES
- MLA
- methyllycaconitine
- nAChR
- nicotinic ACh receptor
- rflp
- restriction fragment length polymorphism
- Received June 6, 1997.
- Accepted November 7, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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