Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats
Cannabinoid CB1 receptor antagonist rimonabant disrupts nicotine reward-associated memory in rats
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DOI：
10.1016/j.pbb.2011.06.019
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Wang, Ji-Shi
中科院分区：
文献类型：
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作者：
Fang, Qin;Li, Fang-Qiong;Wang, Ji-Shi
暴露于先前与药物摄入相关的线索，通过激活先前获得的记忆导致复发。基于以前的研究结果，其中大麻素CB 1受体被发现是至关重要的参与学习和记忆的特定方面，我们研究了CB 1受体在尼古丁奖励记忆中的作用，使用大鼠条件性位置偏好（CPP）模型。在实验1中，通过交替注射尼古丁（0.5 mg/kg，s.c.）和生理盐水来获得尼古丁条件记忆。为了检查利莫那班对尼古丁奖赏记忆的再巩固的作用，将大鼠施用利莫那班（0、0.3和3.0mg/kg，i. p.）在再次暴露于药物配对环境后立即。在实验2中，与实验1类似地对大鼠进行CPP训练。为了检测利莫那班对尼古丁奖赏记忆恢复的影响，利莫那班（0、0.3和3.0 mg/kg.注射用）在尼古丁诱导的CPP恢复试验前给药。在实验3中，为了评估利莫那班本身是否产生奖励记忆，通过交替注射不同剂量的利莫那班（0、0.3和3.0 mg/kg）和盐水来训练大鼠的CPP。3.0 mg/kg剂量的利莫那班显著破坏尼古丁记忆的再巩固，并显著阻断尼古丁诱导的CPP的恢复。然而，利莫那班本身不产生CPP。这些发现提供了明确的证据表明，CB 1受体在尼古丁奖赏记忆中发挥作用，表明CB 1受体拮抗剂可能是管理尼古丁成瘾的潜在靶点。(C)2011 Elsevier Inc. All rights reserved.
Exposure to cues previously associated with drug intake leads to relapse by activating previously acquired memories. Based on previous findings, in which cannabinoid CB1 receptors were found to be critically involved in specific aspects of learning and memory, we investigated the role of CB1 receptors in nicotine reward memory using a rat conditioned place preference (CPP) model. In Experiment 1, rats were trained for CPP with alternating injections of nicotine (0.5 mg/kg, s.c.) and saline to acquire the nicotine-conditioned memory. To examine the effects of rimonabant on the reconsolidation of nicotine reward memory, rats were administered rimonabant (0, 0.3, and 3.0 mg/kg, i.p.) immediately after reexposure to the drug-paired context. In Experiment 2, rats were trained for CPP similarly to Experiment 1. To examine the effects of rimonabant on the reinstatement of nicotine reward memory, rimonabant (0, 0.3, and 3.0 mg/kg. i.p.) was administered before the test of nicotine-induced CPP reinstatement. In Experiment 3, to evaluate whether rimonabant itself produces a reward memory, rats were trained for CPP with alternating injections of different doses of rimonabant (0, 0.3, and 3.0 mg/kg) and saline. Rimonabant at a dose of 3.0 mg/kg significantly disrupted the reconsolidation of nicotine memory and significantly blocked the reinstatement of nicotine-induced CPP. However, rimonabant itself did not produce CPP. These findings provide clear evidence that CB1 receptors play a role in nicotine reward memory, suggesting that CB1 receptor antagonists may be a potential target for managing nicotine addiction. (C) 2011 Elsevier Inc. All rights reserved.