Tolerance to the convulsions induced by daily nicotine treatment in rats

Development of tolerance to the nicotine-induced convulsions in rats was examined. Acute intraperitoneal (i.p.) administration of nicotine (2.5, 3.75 and 5 mg/kg) produced convulsions in a dose-dependent manner. Mecamylamine (1 mg/kg, i.p.) antagonized the convulsions, but hexamethonium (5 mg/kg, i.p.) did not modify them. Daily nicotine administration (2.5, 3.75 and 5 mg/kg, i.p.) once a day for 6 days developed tolerance to the convulsions induced by nicotine. After the daily administrations of nicotine for 6 days, the effects of a challenge administration of nicotine (2 mg/kg) on the nicotine-induced convulsions were tested on the 7th-day. Further tolerances were also developed by the 7th-day challenge administration. After the 7th-day test, nicotine levels of the brain and blood 15 min after the challenge injection were measured. With nicotine (5 mg/kg once a day)-treatment, nicotine levels of all the brain regions were increased. In contrast, a similar challenge injection had no effect on blood nicotine level. These results indicate that the development of tolerance to the nicotine-induced convulsions is produced relatively earlier and day by day by daily administrations to rats, which is closely related with the increase in brain nicotine level.