L-Methamphetamine and selective MAO inhibitors decrease morphine-reinforced and non-reinforced behavior in rats; Insights towards selegiline's mechanism of action
L-Methamphetamine and selective MAO inhibitors decrease morphine-reinforced and non-reinforced behavior in rats; Insights towards selegiline's mechanism of action
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DOI：
10.1016/j.pbb.2006.10.022
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发表时间：
2006-12-01
影响因子：
3.6
通讯作者：
Grasing, Kenneth
中科院分区：
文献类型：
--
作者：
He, Shuangteng;Grasing, Kenneth
司来吉兰是一种B型单胺氧化酶（monoamine oxidase，MAO）抑制剂，具有精神兴奋作用，可减少吗啡的强迫和非增强反应。本研究旨在比较单胺氧化酶抑制和司来吉兰的主要精神兴奋剂代谢物L-甲基苯丙胺治疗对这些行为的影响。在大鼠获得稳定的吗啡自我给药模式后，在渐进比例时间表下，用溶媒、L-甲基苯丙胺、氯吉兰（MAO-A的选择性抑制剂）或雷沙吉兰（MAO-B的选择性抑制剂）开始长期治疗;两种MAO抑制剂均以对一种MAO亚型具有选择性的剂量和抑制两种亚型的较高剂量给药。通过吗啡自我给药和戒断维持阿片类药物依赖，对大鼠进行长达4个周期的评价，记录消退反应。大多数行为措施（92.4%）没有不同的动物在最初和随后的依赖和撤回周期的评价。所有活性治疗都减弱了消退期间的非增强反应。吗啡强化也减少了三个积极的治疗，但更大和更长的影响，观察后抑制MAO-B与雷沙吉兰。无论是线索或吗啡诱导的恢复过程中的反应衰减氯吉兰或雷沙吉兰在非选择性剂量给药，但不是由任一化合物在选择性剂量水平给药。L-甲基苯丙胺对提示诱发的再诱发反应无显著影响，但可降低吗啡诱发的再诱发反应中的非强化反应。这些发现表明，吗啡强化和不同的非强化行为在其对精神兴奋剂治疗或单胺氧化酶抑制的敏感性方面存在很大差异。爱思唯尔公司出版
Selegiline is an inhibitor of type B monoamine oxidase (MAO) with psychostimulant effects that can decrease morphine-rein forced and non-reinforced responding. The present study was undertaken to compare the effects of MAO inhibition and treatment with L-methamphetamine, the major psychostimulant metabolite of selegiline, on these behaviors. After rats acquired a stable pattern of morphine self-administration under a progressive ratio schedule, chronic treatment was initiated with vehicle, L-methamphetamine, clorgyline (a selective inhibitor of MAO-A), or rasagiline (a selective inhibitor of MAO-B); with both MAO inhibitors administered at a dose selective for one MAO isoform and a higher dose that inhibited both isoforms. Rats were evaluated for up to four cycles of opiate dependence maintained by morphine self-administration and withdrawal during, which extinction responding was recorded. Most behavioral measures (92.4%) did not differ in animals evaluated during an initial and subsequent cycles of dependence and withdrawal. All active treatments attenuated non-reinforced responding during extinction. Morphine reinforcement was also decreased by each of the three active treatments, but greater and more prolonged effects were observed following inhibition of MAO-B with rasagiline. Responding during either cue- or morphine-induced reinstatement was attenuated by either clorgyline or rasagiline administered at nonselective doses, but not by either compound administered at selective dose levels. Treatment with L-methamphetamine did not produce sigificant effects on cue-induced reinstatement, but decreased non-reinforced responding during morphine-induced reinstatement. These findings indicate that morphine reinforcement and different non-reinforced behaviors differ greatly in their susceptibility to modification by psychostimulant treatment or MAO inhibition. Published by Elsevier Inc.