Repeated intracerebroventricular infusion of nicotine prevents kainate-induced neurotoxicity by activating the α7 nicotinic acetylcholine receptor

SummaryWe examined whether (−)-nicotine infusion can affect kainic acid (KA)-induced neurotoxicity in rats. Although treatment with a single nicotine infusion (0.5 or 1.0 μg/side, i.c.v.) failed to attenuate KA-induced neurotoxicity, repeated nicotine infusions (1.0 μg/side/day for 10 days) attenuated the seizures, the severe loss of cells in hippocampal regions CA1 and CA3, the increase in activator protein (AP)-1 DNA binding activity, and mortality after KA administration. α-Bungarotoxin and mecamylamine blocked the neuroprotective effects of nicotine. These results suggest that repeated nicotine treatment provides α7 nicotinic acetylcholine receptor-mediated neuroprotection against KA toxicity.