Effects of blockade of α4β2 and α7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats
Effects of blockade of α4β2 and α7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats
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DOI：
10.1017/s1461145713000874
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发表时间：
2014-01-01
影响因子：
4.8
通讯作者：
Liu, Xiu
中科院分区：
文献类型：
--
作者：
Liu, Xiu
暴露于以尼古丁消耗为条件的环境刺激是导致吸烟复发率高的关键因素。我们以前的工作表明，非选择性阻断烟碱乙酰胆碱受体（nAChRs）逆转了线索诱导的尼古丁寻求的恢复，表明胆碱能神经传递在尼古丁线索的条件刺激特性的介导中的作用。本研究进一步研究了两个主要的nAChR亚型，42和7，在线索诱导恢复尼古丁寻求的相对作用。对雄性Sprague-Dawley大鼠进行训练，以按照固定比例5强化方案静脉内自我给予尼古丁（0.03 mg/kg/输注，游离碱）。通过将感官刺激与每次尼古丁输注相关联来建立尼古丁条件性提示。尼古丁维持的反应熄灭后，通过扣留尼古丁输注及其配对的线索，恢复测试会话进行了重新介绍的线索，但没有尼古丁的可用性。在实验前30分钟，大鼠被给予42-选择性拮抗剂二氢-β-赤藓定（DHE）和7-选择性拮抗剂甲基乌头碱（MLA）。预处理MLA，但不是DHE，显着降低的幅度线索诱导的恢复反应的活性，以前尼古丁加强杠杆。在不同的大鼠组中，MLA既不改变尼古丁自我给药，也不改变线索诱导的觅食恢复。这些结果表明，激活7 nAChRs参与尼古丁线索的条件刺激特性的调解，并表明7 nAChRs可能是一个有前途的目标，用于预防线索诱导的吸烟复发的药物开发。
Exposure to environmental stimuli conditioned to nicotine consumption critically contributes to the high relapse rates of tobacco smoking. Our previous work demonstrated that non-selective blockade of nicotinic acetylcholine receptors (nAChRs) reversed the cue-induced reinstatement of nicotine seeking, indicating a role for cholinergic neurotransmission in the mediation of the conditioned incentive properties of nicotine cues. The present study further examined the relative roles of the two major nAChR subtypes, 42 and 7, in the cue-induced reinstatement of nicotine seeking. Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03mg/kg/infusion, free base) on a fixed-ratio 5 schedule of reinforcement. A nicotine-conditioned cue was established by associating a sensory stimulus with each nicotine infusion. After nicotine-maintained responding was extinguished by withholding the nicotine infusion and its paired cue, reinstatement test sessions were conducted with re-presentation of the cue but without the availability of nicotine. Thirty minutes before the tests, the rats were administered the 42-selective antagonist dihydro--erythroidine (DHE) and 7-selective antagonist methyllycaconitine (MLA). Pretreatment with MLA, but not DHE, significantly reduced the magnitude of the cue-induced reinstatement of responses on the active, previously nicotine-reinforced lever. In different sets of rats, MLA altered neither nicotine self-administration nor cue-induced reinstatement of food seeking. These results demonstrate that activation of 7 nAChRs participates in the mediation of the conditioned incentive properties of nicotine cues and suggest that 7 nAChRs may be a promising target for the development of medications for the prevention of cue-induced smoking relapse.