Pharmacological Characterization of Nicotine-Induced Seizures in Mice1

Pharmacological mechanisms involved in nicotine-induced sei-zures were investigated in mice by testing the ability of several nicotinic agonists in producing seizures after peripheral admin-istration. In addition, nicotinic antagonists such as hexametho-nium, mecamylamine, dihydro-b-erythroidine, and methyllyca-conitine citrate (MLA) were used in combination with nicotine. We also examined the involvement of calcium channels, N-methyl-D-aspartate receptors, and nitric oxide formation in nic-otine-induced seizures. Our results showed that the peripheral administration of nicotine produced seizures in a stereospecific and mecamylamine-sensitive manner. Nicotine-induced sei-zures are centrally mediated and involve the activation of a7 along with other nicotinic receptor subunits. Indeed, MLA, an a7-antagonist, blocked the effects of nicotine after periphera