Addiction Biology Unit (ABU), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Psychopharmacology (Berl). 2010 Oct;212(3):321-8. doi: 10.1007/s00213-010-1957-x. Epub 2010 Jul 31.
We recently demonstrated that blocking specific nicotinic acetylcholine receptors (nAChRs) abolishes the conditioned reinforcing properties of ethanol-associated cues in rat, suggesting nAChRs as promising pharmacological targets for prevention of cue-induced relapse.
The present study investigated the involvement of nAChR subtypes in the conditioned reinforcing properties of stimuli associated with a natural reward (sucrose).
Water-deprived rats were trained to associate a tone + light stimulus (CS) with the presentation of a 0.1 M sucrose solution for 10 consecutive days. On the subsequent day, the animals were tested on the stringent acquisition of a new instrumental response with conditioned reinforcement, following a systemic injection of the nonselective nAChR antagonist mecamylamine (MEC) or the selective α7 and α6/α3β2β3* nAChR antagonist methyllycaconitine (MLA). At testing, the rats were presented with two novel levers. Responding on the lever assigned as active (CR lever) resulted in a presentation of the CS alone, while pressing the inactive lever (NCR lever) had no programmed consequences.
Control animals pressed the CR lever significantly more than the NCR lever, demonstrating that the CR had acquired conditioned reinforcing properties. Systemic MEC as well as MLA reduced the CR lever responses to the same level as for the NCR lever.
These results demonstrate a role for the α7 and/or α6/α3β2β3* nAChRs in conditioned reinforcement to a natural reward and suggest neuronal nAChRs as common mediators of the impact of cues on incentive processes.
我们最近的研究表明,阻断特定的烟碱型乙酰胆碱受体(nAChRs)可消除大鼠乙醇相关线索的条件强化作用,这表明 nAChRs 是预防线索诱导复吸的有前途的药物靶点。
本研究旨在探讨 nAChR 亚型在与自然奖赏(蔗糖)相关刺激的条件强化作用中的作用。
将缺水的大鼠训练为将音调+灯光刺激(CS)与 0.1 M 蔗糖溶液的呈现相关联,连续 10 天。在随后的一天,动物在系统注射非选择性烟碱型乙酰胆碱受体拮抗剂美加仑(MEC)或选择性 α7 和 α6/α3β2β3*烟碱型乙酰胆碱受体拮抗剂甲基戊基甲二烯羟酸(MLA)后,接受了一个新的与条件强化相关的工具性反应的严格获取测试。在测试中,向大鼠呈现两个新的杠杆。在被分配为主动的杠杆(CR 杠杆)上进行反应会导致 CS 单独呈现,而按压不活跃的杠杆(NCR 杠杆)没有编程后果。
对照动物按压 CR 杠杆的次数明显多于 NCR 杠杆,表明 CR 已经获得了条件强化作用。系统给予 MEC 以及 MLA 会将 CR 杠杆反应降低到与 NCR 杠杆相同的水平。
这些结果表明,α7 和/或 α6/α3β2β3* nAChRs 在自然奖赏的条件强化中起作用,并表明神经元 nAChRs 是线索对激励过程影响的共同介质。