Reduction in methamphetamine induced sensitization and reinstatement after combined pergolide plus ondansetron treatment during withdrawal
Reduction in methamphetamine induced sensitization and reinstatement after combined pergolide plus ondansetron treatment during withdrawal
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DOI：
10.1016/j.ejphar.2007.02.056
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发表时间：
2007-06-22
影响因子：
5
通讯作者：
Ellinwood, Everett H.
中科院分区：
文献类型：
--
作者：
Davidson, Colin;Gopalan, Rupa;Ellinwood, Everett H.
我们以前已经发现，5-HT 3受体拮抗剂昂丹司琼是有用的，在减少可卡因自我管理和可卡因诱导的致敏作用，在可卡因戒断期间给予大鼠。最近，我们发现多巴胺激动剂培高利特加昂丹司琼的组合，3.5小时后，逆转可卡因致敏和相关的NMDA和AMPA受体的变化。在此，我们在1）甲基苯丙胺致敏模型和2）静脉内甲基苯丙胺自我给药后使用鼻子戳任务的恢复模型中测试了该药物组合。我们发现培高利特加昂丹司琼在甲基苯丙胺戒断的第3-7天给药可以逆转甲基苯丙胺诱导的致敏作用并减弱复吸。我们假设培高利特可能会引起甲基苯丙胺相关的记忆，昂丹司琼可以破坏其再巩固。这些数据表明，培高利特加昂丹司琼治疗可能是一种有用的治疗，以减少甲基苯丙胺滥用者的复发。(c)2007 Elsevier B. V.保留所有权利。
We have previously found the 5-HT3 receptor antagonist ondansetron to be useful in reducing cocaine self-administration and cocaine induced sensitization in rats when given during cocaine withdrawal. More recently we have found the combination of the dopamine agonist pergolide plus ondansetron, 3.5 h later, to reverse cocaine sensitization and associated changes in NMDA and AMPA receptors. Here we tested this drug combination in 1) a methamphetamine sensitization model and 2) a reinstatement model after intravenous methamphetamine self-administration using a nose-poke task. We found pergolide plus ondansetron given from days 3-7 of methamphetamine withdrawal to reverse methamplictamine induced sensitization and attenuate reinstatement. We hypothesize that pergolide may evoke a methamphetamine associated memory and that ondansetron can disrupt its reconsolidation. These data suggest that pergolide plus ondansetron treatment may be useful as a therapy to reduce relapse in methamphetamine abusers. (c) 2007 Elsevier B.V. All rights reserved.