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Varenicline provokes impulsive action by stimulating α4β2 nicotinic acetylcholine receptors in the infralimbic cortex in a nicotine exposure status-dependent manner

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Title: Varenicline provokes impulsive action by stimulating α4β2 nicotinic acetylcholine receptors in the infralimbic cortex in a nicotine exposure status-dependent manner
Authors: Ohmura, Yu Browse this author →KAKEN DB
Sasamori, Hitomi Browse this author
Tsutsui-Kimura, Iku Browse this author
Izumi, Takeshi Browse this author →KAKEN DB
Yoshida, Takayuki Browse this author →KAKEN DB
Yoshioka, Mitsuhiro Browse this author →KAKEN DB
Keywords: Impulsive behavior
Chantix
Champix
Tobacco
Attention
Issue Date: Mar-2017
Publisher: Elsevier
Journal Title: Pharmacology biochemistry and behavior
Volume: 154
Start Page: 1
End Page: 10
Publisher DOI: 10.1016/j.pbb.2017.01.002
PMID: 28087221
Abstract: Higher impulsivity is a risk factor for criminal involvement and drug addiction. Because nicotine administration enhances impulsivity, the effects of stop-smoking aids stimulating nicotinic acetylcholine receptors (nAChRs) on impulsivity must be determined in different conditions. Our goals were 1) to confirm the relationship between varenicline, a stop-smoking aid and α4β2 nAChR partial agonist, and impulsivity, 2) to elucidate the mechanisms underlying the effects of varenicline, 3) to examine whether a low dose of varenicline that does not evoke impulsive action could block the stimulating effects of nicotine on impulsive action, 4) to determine whether the route of administration could modulate the effects of varenicline on impulsive action, and 5) to determine whether the effects of varenicline on impulsivity could be altered by smoking status. We used a 3-choice serial reaction time task to assess impulsivity and other cognitive functions in rats. Our findings are as follows: 1) acute subcutaneous (s.c.) injection of varenicline evoked impulsive action in a dose-dependent manner; 2) the effects of varenicline on impulsivity were blocked by the microinjection of dihydro-β-erythroidine, a α4β2 nAChR antagonist, into the infralimbic cortex; 3) the low dose of varenicline did not attenuate the effects of nicotine on impulsive action at all; 4) oral administration of varenicline evoked impulsive action in a similar manner to s.c. injection; and 5) the stimulating effects of varenicline on impulsive action were not observed in rats that received nicotine infusion for 8 days or nicotine-abstinent rats after discontinuing infusion. Additionally, we found that oral varenicline administration enhanced attentional function whether nicotine was infused or not. Thus, although varenicline administration could be harmless to heavy smokers or ex-smokers, it could be difficult for non-smokers with respect to impulsivity, whereas it may be beneficial with respect to attentional function.
Rights: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/68397
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大村 優

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