title: Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons.
abstract: Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of epileptic disorders; however, the mechanisms of nACh receptors in seizure generation remain unknown. Here, we performed behavioral and immunohistochemical studies in mice and rats to clarify the mechanisms underlying nicotine-induced seizures. Treatment of animals with nicotine (1-4 mg/kg, i.p.) produced motor excitement in a dose-dependent manner and elicited convulsive seizures at 3 and 4 mg/kg. The nicotine-induced seizures were abolished by a subtype non-selective nACh antagonist, mecamylamine (MEC). An α7 nACh antagonist, methyllycaconitine, also significantly inhibited nicotine-induced seizures whereas an α4β2 nACh antagonist, dihydro-β-erythroidine, affected only weakly. Topographical analysis of Fos protein expression, a biological marker of neural excitation, revealed that a convulsive dose (4 mg/kg) of nicotine region-specifically activated neurons in the piriform cortex, amygdala, medial habenula, paratenial thalamus, anterior hypothalamus and solitary nucleus among 48 brain regions examined, and this was also suppressed by MEC. In addition, electric lesioning of the amygdala, but not the piriform cortex, medial habenula and thalamus, specifically inhibited nicotine-induced seizures. Furthermore, microinjection of nicotine (100 and 300 μg/side) into the amygdala elicited convulsive seizures in a dose-related manner. The present results suggest that nicotine elicits convulsive seizures by activating amygdalar neurons mainly via α7 nACh receptors.
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Higor A
authors.initials: HA
authors.lastname: Iha
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kunisawa
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokudome
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical SciencesOsaka, Japan; Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto UniversityKyoto, Japan; Department of Neurology, Graduate School of Medicine, Wakayama Medical UniversityWakayama, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kinboshi
authors.affiliation: Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University Kyoto, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Neurology, Graduate School of Medicine, Wakayama Medical University Wakayama, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ohno
keywords: Fos expression; amygdala; convulsive seizures; nicotine; nicotinic acetylcholine receptors