PT - JOURNAL ARTICLE AU - Jerry A. Stitzel AU - Melissa Jimenez AU - Michael J. Marks AU - Theresa Tritto AU - Allan C. Collins TI - Potential Role of the α4 and α6 Nicotinic Receptor Subunits in Regulating Nicotine-Induced Seizures DP - 2000 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 67--74 VI - 293 IP - 1 4099 - http://jpet.aspetjournals.org/content/293/1/67.short 4100 - http://jpet.aspetjournals.org/content/293/1/67.full SO - J Pharmacol Exp Ther2000 Apr 01; 293 AB - Several studies have shown that genetic factors influence sensitivity to nicotine-induced seizures in the mouse. We used recombinant inbred (RI) strains derived from the Long-Sleep (LS) and Short-Sleep (SS) mouse lines to assess the possibility that polymorphisms associated with one or more of the nicotinic receptors cosegregate with differential sensitivity to nicotine-induced seizures. Restriction fragment length polymorphisms (RFLPs) associated with the α2, α3, α4, α5, and α6 nicotinic receptors were identified in the LS and SS mouse lines, but the RI strains were polymorphic for only the α4 and α6 RFLPs. The RI strains were tested for sensitivity to nicotine-induced seizures. Strain and gender effects on seizure sensitivity were obtained as assessed by ED50 values and latency to seizure. Those RI strains with the LS-like α4 RFLP were, on average, more sensitive to nicotine-induced seizures than were those RI strains with SS-like α4 RFLP. The α6 nicotine receptor may also play a role in modulating nicotine-induced seizures, but this effect is markedly influenced by gender. Females of the RI strains with the LS-like α6 RFLP were more sensitive to nicotine than were females of the strains with the SS-like α6 RFLP. Similar trends were seen in the males, but these trends were not significant. Thus, these strain differences may be due to polymorphisms associated with both the α4 and α6 nicotinic receptors, but gender also plays an important role in regulating sensitivity to nicotine-induced seizure. The American Society for Pharmacology and Experimental Therapeutics