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Iha HA, Kunisawa N, Shimizu S, et al. Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons. Front Pharmacol. 2017;8:57doi: 10.3389/fphar.2017.00057.
Iha, H. A., Kunisawa, N., Shimizu, S., Tokudome, K., Mukai, T., Kinboshi, M., Ikeda, A., Ito, H., Serikawa, T., & Ohno, Y. (2017). Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons. Frontiers in pharmacology, 857. https://doi.org/10.3389/fphar.2017.00057
Iha, Higor A, et al. "Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons." Frontiers in pharmacology vol. 8 (2017): 57. doi: https://doi.org/10.3389/fphar.2017.00057
Iha HA, Kunisawa N, Shimizu S, Tokudome K, Mukai T, Kinboshi M, Ikeda A, Ito H, Serikawa T, Ohno Y. Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons. Front Pharmacol. 2017 Feb 09;8:57. doi: 10.3389/fphar.2017.00057. eCollection 2017. PMID: 28232801; PMCID: PMC5298991.
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Front Pharmacol. 2017 Feb 09;8:57. doi: 10.3389/fphar.2017.00057. eCollection 2017.

Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons.

Frontiers in pharmacology

Higor A Iha, Naofumi Kunisawa, Saki Shimizu, Kentaro Tokudome, Takahiro Mukai, Masato Kinboshi, Akio Ikeda, Hidefumi Ito, Tadao Serikawa, Yukihiro Ohno

Affiliations

  1. Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences Osaka, Japan.
  2. 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.
  3. Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University Kyoto, Japan.
  4. Department of Neurology, Graduate School of Medicine, Wakayama Medical University Wakayama, Japan.

PMID: 28232801 PMCID: PMC5298991 DOI: 10.3389/fphar.2017.00057

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.

Keywords: Fos expression; amygdala; convulsive seizures; nicotine; nicotinic acetylcholine receptors

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