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
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
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DOI：
10.1016/j.pbb.2012.03.006
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发表时间：
2012-06-01
影响因子：
3.6
通讯作者：
Rodd, Zachary A.
中科院分区：
文献类型：
--
作者：
Deehan, Gerald A., Jr.;McKinzie, David L.;Rodd, Zachary A.
目前的研究评估了选择性κ阿片拮抗剂JDTic对酒精（EtOH）寻求行为，EtOH复发和EtOH维持反应的影响。成年酒精偏好（P）大鼠在2杠杆操作室训练，自我管理15%乙醇（v/v）的固定比例5（FR-5）和水的FR-1强化时间表在1小时的会议。10周后，大鼠进行了7次灭绝训练。然后将大鼠在不接触EtOH的情况下在其饲养笼中饲养3周。所有大鼠接受注射（s.c.）0、1、3或10 mg/kg JDTic（n = 11 - 14/组）。然后使用巴甫洛夫自发恢复范例（PSR;酒精寻求的动物模型）测试大鼠四个阶段，在此期间，记录对EtOH和水杠杆的反应，但不产生它们各自的应答。PSR试验后，在开始EtOH复发试验前一周，将大鼠放回其饲养笼中，不接触EtOH。为了检查EtOH复发反应，将大鼠返回到操作室，并且EtOH（FR 5）和水（FR 1）杠杆处于活动状态。最后，在17个操作阶段对大鼠进行测试，以评估JDTic对EtOH维持反应的影响。在初始维持期前30分钟，大鼠接受0、1、3或10 mg/kg JDTic（从初始实验中平衡）。在测试前14和25天给予JDTic剂量依赖性地降低了EtOH PSR的表达和复发反应。相比之下，JDTic没有改变EtOH响应在维护条件下。总体而言，本研究的结果表明，在复发和维持条件下，不同的机制介导EtOH自我给药，κ阿片受体参与介导EtOH寻求行为和复发反应，但不参与持续的EtOH自我给药。(C)2012 Elsevier Inc. All rights reserved.
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. (C) 2012 Elsevier Inc. All rights reserved.