Methamphetamine self-administration and the effect of contingency on monoamine and metabolite tissue levels in the rat
Methamphetamine self-administration and the effect of contingency on monoamine and metabolite tissue levels in the rat
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DOI：
10.1016/j.brainres.2009.11.069
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发表时间：
2010-03-04
期刊：
影响因子：
2.9
通讯作者：
Schenk, Susan
中科院分区：
文献类型：
--
作者：
Brennan, Katharine A.;Colussi-Mas, Joyce;Schenk, Susan
大量研究表明，暴露于大剂量甲基苯丙胺(MA)会对中枢多巴胺(DA)和5-羟色胺(5-HT)神经元产生毒性。然而，在大多数这些研究中，高剂量的MA是在较短的暴露时间内由实验者给予的。由于偶然性是药物暴露的许多影响的决定因素，目前的目标是调查短期(24小时)或较长时间(7天)戒断后自我给药MA对组织单胺水平的影响。正如先前报道的那样，非偶然的“狂欢”大剂量治疗方案(每2小时注射4次10 mg/kg的MA)导致皮质5-羟色胺和纹状体DA的持续耗竭。然后在连续20天后测定自身注射MA(0.1 mg/kg/次)的效果，其中采用颈套设计，即一些大鼠在操作杆按压下接受MA，而其他大鼠则根据随机大鼠的反应接受MA或生理盐水。自我给药的MA产生了一过性纹状体DA耗竭，DA周转持续增加，表明存在一些持久的适应。此外，轭设计表明，偶然性对这些参数没有影响。(C)2009年，爱思唯尔出版。
A number of studies have shown that exposure to high doses of methamphetamine (MA) is toxic to central dopamine (DA) and serotonin (5-HT) neurons. In most of those studies, however, high doses of MA were experimenter-administered during a short exposure time. Because contingency is a determinant for many effects of drug exposure, the present objective was to investigate the effects of self-administered MA on tissue monoamine levels following a short (24 hours) or longer (7 days) withdrawal period. As previously reported, a noncontingent "binge" high-dose treatment regimen (4 injections of 10 mg/kg MA administered every 2 hours) produced persistent depletion of cortical 5-HT and striatal DA. Effects of self-administered MA (0.1 mg/kg/infusion) were then determined following a 20-day duration where a yoked design was employed such that some rats received MA contingent on an operant lever press and others received either MA or saline dependent on the responses of the contingent rat. Self-administered MA produced a transient striatal DA depletion with a more persistent increase in DA turnover, indicating the presence of some lasting adaptations. Furthermore, the yoked design revealed that there was no effect of contingency on these parameters. (C) 2009 Published by Elsevier B.V.