JDTic，一种κ阿片受体拮抗剂，对雌性酒精偏好（P）大鼠觅酒行为表达和复饮的持久影响。
The long-lasting effects of JDTic, a kappa opioid receptor antagonist, on the expression of ethanol-seeking behavior and the relapse drinking of female alcohol-preferring (P) rats.
机构信息
Department of Psychiatry, Institute of Psychiatric Research, Indiana School of Medicine, Indianapolis, IN 46202, USA.
出版信息
Pharmacol Biochem Behav. 2012 Jun;101(4):581-7. doi: 10.1016/j.pbb.2012.03.006. Epub 2012 Mar 10.
The current study assessed the effects of the selective kappa opioid antagonist JDTic on alcohol (EtOH)-seeking behavior, EtOH relapse, and maintenance responding for EtOH. Adult alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% EtOH (v/v) on a fixed-ratio 5 (FR-5) and water on a FR-1 schedule of reinforcement during 1-hr sessions. After 10 weeks, rats underwent extinction training for seven sessions. Rats were then maintained in their home cages for 3 weeks without EtOH access. All rats received an injection (s.c.) of 0, 1, 3, or 10 mg/kg JDTic (n=11-14/group) after the first week of the home cage period. Rats were then tested using the Pavlovian Spontaneous Recovery paradigm (PSR; an animal model of alcohol-seeking) for four sessions during which, responses on the EtOH and water levers were recorded but did not produce their respective reinforcer. Following PSR testing rats were returned to their home cages without access to EtOH for one week prior to the start of EtOH relapse testing. To examine EtOH relapse responding, rats were returned to the operant chambers and the EtOH (FR5) and water (FR1) levers were active. Finally, rats were then tested over 17 operant sessions to assess the effects of JDTic on maintenance responding for EtOH. Rats received 0, 1, 3, or 10 mg/kg JDTic (counterbalanced from the initial experiment) 30 minutes prior to the initial maintenance session. JDTic administered 14 and 25 days prior to testing dose-dependently reduced the expression of an EtOH PSR and relapse responding. In contrast, JDTic did not alter EtOH responding under maintenance conditions. Overall, the results of this study indicate that different mechanisms mediate EtOH self-administration under relapse and maintenance conditions and kappa opioid receptors are involved in mediating EtOH-seeking behavior and relapse responding but not on-going EtOH self-administration.
本研究评估了选择性 κ 阿片受体拮抗剂 JDTic 对酒精（EtOH）觅药行为、EtOH 复吸和 EtOH 维持反应的影响。成年酒精偏好（P）大鼠在 2 臂操作室中接受训练，以 FR-5 的固定比率自我给予 15% EtOH（v/v），并以 FR-1 的强化时间表自我给予水，每次 1 小时。在 10 周后，大鼠接受了 7 个疗程的消退训练。然后，大鼠在没有 EtOH 摄入的情况下被维持在其原笼中 3 周。所有大鼠在原笼期的第一周后接受 0、1、3 或 10 mg/kg JDTic 的皮下注射（n=11-14/组）。然后，大鼠使用 Pavlovian Spontaneous Recovery 范式（PSR；一种酒精觅药的动物模型）进行了 4 个疗程的测试，在此期间，记录了 EtOH 和水杠杆上的反应，但没有产生各自的强化物。PSR 测试后，大鼠被送回原笼，在开始 EtOH 复吸测试前一周内没有接触 EtOH。为了检查 EtOH 复吸反应，大鼠被送回操作室，EtOH（FR5）和水（FR1）杠杆处于活动状态。最后，大鼠在 17 个操作疗程中接受测试，以评估 JDTic 对 EtOH 维持反应的影响。大鼠在初始维持疗程前 30 分钟接受 0、1、3 或 10 mg/kg JDTic（与初始实验平衡）。在测试前 14 天和 25 天给予 JDTic 剂量依赖性地降低了 EtOH PSR 和复吸反应的表达。相比之下，JDTic 并未改变维持条件下的 EtOH 反应。总体而言，这项研究的结果表明，不同的机制介导了复吸和维持条件下的 EtOH 自我给药，κ 阿片受体参与了介导 EtOH 觅药行为和复吸反应，但不参与持续的 EtOH 自我给药。
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