Chronic nicotine pretreatment protects the blood-brain barrier against nicotine-induced seizures in the rat

This study was designed to investigate the possible protective actions of nicotine on cerebrovascular permeability in convulsions during nicotine-induced seizures. We have measured the permeability changes in the blood-brain barrier (BBB) macroscopically and spectrophotometrically by using Evans blue dye. Specific gravity measurements were also performed to assess brain edema which develops after blood-brain barrier opening. The experiments were carried out on Wistar rats. Rats were divided into two groups. They received acutely a convulsive dose of nicotine 3, 5, 8 and 9 mg kg(-1) i.p. or pretreated with a low dose of nicotine (0.8 mg kg(-1) i.p.) for 21 days followed by the procedure mentioned in the first group. Acute nicotine injection induced a significant increase in blood pressure and Evans-blue passage, despite a decline in specific gravity values. Low doses of chronic nicotine administration markedly reduced both the leakage of dye, and brain water content. Chronic treatment with low doses of nicotine (0.8 mg kg(-1) day(-1) s.c.) lessened the intensity of tonic-clonic seizures observed with a single dose of 3, 5, 8 or 9 mg kg-l nicotine. The data presented here demonstrate that nicotine pretreatment results in decreased sensitivity to nicotine-induced seizures in rats. (C) 1999 Academic Press