Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors.
Nicotine-induced seizure sensitivity was assessed in 19 inbred mouse strains. Two routes of drug administration were utilized: acute intravenous (IV) infusion and intraperitoneal (IP) injection. Dose-response curves for sensitivity to IP nicotine-induced seizures were constructed for the 19 inbred strains and a heterogeneous stock (HS/Ibg) of mice. Differences were observed among the strains both in ED50 values and slopes of the dose-response curves following IP injection of nicotine. ST/bJ mice were the most sensitive having an ED50 of 2.34 +/- 0.09 mg/kg nicotine. DBA/1J mice were the most resistant strain with an ED50 value of 6.16 +/- 0.02 m/kg nicotine. Latency to clonic seizure was measured in the 19 inbred mouse strains using the acute IV route of drug administration. Again, ST/bJ mice were the most sensitive and DBA/2Ibg were the most resistant to IV nicotine-induced seizures. Significant correlations were observed between latency to IV nicotine-induced seizures and both ED50 values and the slope of the dose-response curves for IP nicotine-induced seizures. However, the pattern of results differed between the two routes of drug administration. The relationship between seizure sensitivity and nicotinic receptor concentration in three brain regions, cortex, midbrain and hippocampus, was also assessed using alpha-bungarotoxin (BTX) as the ligand. A significant relationship was observed between BTX binding in the three brain regions and sensitivity to IV nicotine-induced seizures such that strains with greater concentrations of BTX binding sites were more sensitive to nicotine-induced seizures than were strains with lower concentrations of BTX binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Miner
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LL
Department of Psychology, University of Colorado, Boulder 80309.
Collins
A C
AC
D000818:Animals; D001923:Brain Chemistry; D002038:Bungarotoxins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000502:physiology*; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D011930:Reaction Time; D011978:Receptors, Nicotinic / Q000032:analysis*; D012640:Seizures / Q000139:chemically induced / Q000235:genetics*; D013045:Species Specificity
D002038:Bungarotoxins; D011978:Receptors, Nicotinic; D009538:Nicotine