Neuroadaptations in the dopaminergic system after active self-administration but not after passive administration of methamphetamine
Neuroadaptations in the dopaminergic system after active self-administration but not after passive administration of methamphetamine
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DOI：
10.1016/s0014-2999(99)00094-1
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发表时间：
1999-04-29
影响因子：
5
通讯作者：
Goldberg, SR
中科院分区：
文献类型：
--
作者：
Stefanski, R;Ladenheim, B;Goldberg, SR
甲基苯丙胺是一种强烈而持久的兴奋剂，可以很容易地合成，口服，静脉注射或作为“冰”吸烟时都有效。由于滥用程度的不断升级，显然需要实验室程序来评估甲基苯丙胺滥用的动机成分及其潜在的神经生物学机制。在本实验中，我们利用了一个“轭”的程序，其中大鼠在三个组中同时运行，其中两只大鼠作为轭对照，其接受0.1 mg/kg甲基苯丙胺或生理盐水的注射，每次由第三对大鼠自我给药0.1 mg/kg甲基苯丙胺的响应注射时，其不依赖于响应。主动自我给药甲基苯丙胺5周，然后停止给药24小时的大鼠显示腹侧被盖区（34%）和黑质背侧（31%）和内侧（21%）的体树突多巴胺D-2自受体水平显著降低，多巴胺D-2自受体水平相应下调。1受体在壳的核丘脑（15%），在体外定量放射自显影测量。由于多巴胺D-1和D-2受体水平的下降，发生在大鼠自我管理的甲基苯丙胺没有发生在同窝出生的人，无论是轭注射甲基苯丙胺或盐水，这些变化可能反映动机状态时，甲基苯丙胺注射依赖于一个积极的药物自我管理行为。(C)1999 Elsevier Science B. V.保留所有权利。
Methamphetamine is a strong and long-lasting stimulant that can be easily synthesized and is effective when taken either orally, intravenously, or smoked as 'ice'. Due to it's escalating abuse, a clear need exists for laboratory procedures to evaluate motivational components of methamphetamine abuse and their underlying neurobiological mechanisms. In the present experiment, we utilized a 'yoked' procedure in which rats were run simultaneously in groups of three, with two rats serving as yoked controls which received an injection of either 0.1 mg/kg methamphetamine or saline which was not contingent on responding each time a response-contingent injection of 0.1 mg/kg methamphetamine was self-administered by the third paired rat. Rats that had actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed marked decreases in somatodendritic dopamine D-2 autoreceptors levels in the ventral tegmental area (34%) and medial (31%) and dorsal (21%) part of the substantia nigra zona compacta with a corresponding down-regulation of dopamine D-1 receptors in the shell of the nucleus accumbens (15%), as measured by in vitro quantitative autoradiography. Since the decreases in levels of dopamine D-1 and D-2 receptors which occurred in rats self-administering methamphetamine did not occur in littermates that received either yoked injections of methamphetamine or saline, these changes likely reflect motivational states that were present when methamphetamine injection depended an active drug self-administration behavior. (C) 1999 Elsevier Science B.V. All rights reserved.