Effect of nicotine pretreatment on nicotine-induced seizures.

Inactivation of the nicotinic receptor via the process of desensitization has been well characterized for the nicotinic receptor in vitro, but potential behavioral manifestations of desensitization have received little study. To test whether behavioral desensitization occurs, C3H and DBA mice were pretreated with subseizure-producing doses of nicotine and nicotine-induced seizure sensitivity was determined at various time intervals after pretreatment. Fifteen minutes after nicotine pretreatment, DBA mice were significantly less sensitive to nicotine-induced seizures than were saline pretreated mice after both IP and IV administration. Seizure sensitivity returned to baseline levels at 60 minutes after pretreatment for the IP route of administration and at 30 minutes for the IV route of administration. Sensitivity to nicotine-induced seizures was altered for C3H mice under only one experimental condition; 7.5 minutes after IP injection with 2.0 mg/kg nicotine. Thus, DBA mice display a marked behavioral desensitization as a result of nicotine pretreatment whereas C3H mice do not. These results, in conjunction with our previous studies, indicate that nicotine-induced seizure sensitivity may be influenced by a minimum of two factors: the concentration of nicotinic receptors in the brain and possibly the ability of these receptors to inactivate in the presence of nicotine.