Nicotine-induced enhancement of responding for conditioned reinforcement in rats: Role of prior nicotine exposure and α4β2 nicotinic receptors

Nicotine-induced enhancement of responding for conditioned reinforcement in rats: Role of prior nicotine exposure and α4β2 nicotinic receptors
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DOI:
10.1007/s00213-012-2832-8
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发表时间:
2013-01-01
期刊:
影响因子:
3.4
通讯作者:
Fletcher, Paul J.
Fletcher, Paul J.
中科院分区:
医学3区
文献类型:
--
作者:
Guy, Elizabeth Glenn;Fletcher, Paul J.

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与尼古丁相关的刺激可以成为重要的动机,并可能在烟草依赖中发挥作用。以往的研究表明,尼古丁增强了条件反射(CR)的反应。这些研究探讨了先前暴露于尼古丁对CR反应的影响,这种反应的持续性,以及α 4 β 2或α 7烟碱受体亚型的作用。水剥夺大鼠给予13巴甫洛夫条件反射,其中光/声条件刺激(CS)与水的输送配对。然后,向大鼠提供两个杠杆:一个提供CS(现在是CR),另一个不活动。实验研究了巴甫洛夫条件反射会议之前,在CS介绍,操作性响应CR在存在和不存在尼古丁的情况下,和持久性的CR响应的方法行为的尼古丁管理的效果。用美加明拮抗烟碱乙酰胆碱受体(nAChR),用二氢-β-赤藓定(DH β E)或甲基乌头碱(MLA)拮抗α 4 β 2或α 7 nAChR,研究了尼古丁增强的CR反应的影响。在多次试验中,对CR的反应及其尼古丁的增强作用稳定。尼古丁增强了对尼古丁诱导的CR的反应,被美加明和DH β E阻断,但不被MLA阻断。尼古丁增强了巴甫洛夫辨别方法,并显示出敏化尼古丁诱导的CR反应增强,这种效应依赖于α 4 β 2 nAChRs。
Stimuli associated with nicotine can become motivationally significant and may play a role in tobacco dependence. Previous work indicates that nicotine enhances responding for a conditioned reinforcer (CR).These studies examined the effects of prior exposure to nicotine on responding for a CR, persistence of this response, and the role of alpha 4 beta 2 or alpha 7 nicotinic receptor subtypes.Water deprived rats were given 13 Pavlovian conditioning sessions where a light/tone conditioned stimulus (CS) was paired with the delivery of water. Then, rats were presented with two levers: one delivered the CS (now a CR), the other was inactive. Experiments examined the effect of nicotine administered prior to Pavlovian conditioning sessions on approach behavior during CS presentations, operant responding for CR in the presence and absence of nicotine, and the persistence of responding for CR. The effects of nicotinic acetylcholine receptor (nAChR) antagonism with mecamylamine and alpha 4 beta 2 or alpha 7 nAChR antagonism with dihydro-beta-erythroidine (DH beta E) or methyllycaconitine (MLA) on nicotine-enhanced responding for CR were examined.Nicotine enhanced approach behavior during CS presentations and potentiated operant responding for CR, an effect sensitized as a result of nicotine exposure during conditioning. Responding for CR and its potentiation by nicotine was stable over multiple tests. Enhanced responding for the CR induced by nicotine was blocked by mecamylamine and DH beta E, but not MLA.Nicotine enhances Pavlovian discriminated approach and shows sensitized nicotine-induced enhancements in responding for CR, an effect depending on alpha 4 beta 2 nAChRs.