Nicotine evokes kinetic tremor by activating the inferior olive via alpha 7 nicotinic acetylcholine receptors

作者：Kunisawa Naofumi; Iha Higor A; Shimizu Saki; Tokudome Kentaro; Mukai Takahiro; Kinboshi Masato; Serikawa Tadao; Ohno Yukihiro^*

来源：Behavioural Brain Research, 2016, 314: 173-180.

DOI：10.1016/j.bbr.2016.08.013

• Nicotine
• Tremor
• Nicotinic acetylcholine receptors
• Inferior olive
• Fos expression

Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of movement disorders (e.g., tremor) and epilepsy. Here, we performed behavioral and immunohistochemical studies using mice and rats to elucidate the mechanisms underlying nicotine-induced tremor. Treatments of animals with nicotine (0.5-2 mg/kg, i.p.) elicited kinetic tremor, which was completely suppressed by the nACh receptor antagonist mecamylamine (MEC). The specific alpha 7 nACh receptor antagonist methyllycaconitine (MLA) also inhibited nicotine-induced tremor, whereas the alpha 4 beta 2 nACh antagonist dihydro-beta-erythroidine (DH beta E) or the peripheral alpha 3 beta 4 nACh antagonist hexamethonium showed no effects. Mapping analysis of Fos protein expression, a biological marker of neural excitation, revealed that a tremorgenic dose (1 mg/kg) of nicotine region-specifically elevated Fos expression in the piriform cortex (PirC), medial habenula, solitary nucleus and inferior olive (IO) among 44 brain regions examined. In addition, similarly to the tremor responses, nicotine-induced Fos expression in the PirC and IO was selectively antagonized by MLA, but not by DH beta E. Furthermore, an electrical lesioning of the IO, but not the PirC, significantly suppressed the induction of nicotine tremor. The present results suggest that nicotine elicits kinetic tremor in rodents by activating the IO neurons via alpha 7 nACh receptors.

• 出版日期2016-11-1