Anatomical substrates for the discriminative stimulus effects of methamphetamine in rats
Anatomical substrates for the discriminative stimulus effects of methamphetamine in rats
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DOI：
10.1111/j.1471-4159.2004.02705.x
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发表时间：
2004-10-01
影响因子：
4.7
通讯作者：
Nabeshima, T
中科院分区：
文献类型：
--
作者：
Nakajima, A;Yamada, K;Nabeshima, T
甲基苯丙胺是一种精神兴奋剂药物，作用于中枢单胺能神经元，产生急性精神刺激和持久的行为效应，包括成瘾和精神病。药物鉴别程序在描述成瘾药物的主观影响方面特别有用。在本研究中，以确定潜在的解剖学基板的歧视性刺激作用的甲基苯丙胺，我们研究了药物歧视相关的Fos表达在Sprague-Dawley大鼠训练区分甲基苯丙胺从盐水下的两个杠杆固定比例20（FR-20）的时间表的食物强化。在药物辨别试验后2 h，将满足学习辨别标准的大鼠麻醉并灌注，并在15个脑区检查Fos免疫反应性。Fos的表达在大鼠的大脑中，区分甲基苯丙胺从盐水显着增加，在延髓核（NAc）和腹侧被盖区（VTA），但不是在其他地区，包括大脑皮层，尾壳核，黑质，海马，杏仁核和缰核，与表达在对照组大鼠，保持FR-20的时间表。目前的研究结果表明，VTA和NAC作为可能的神经元底物在甲基苯丙胺的歧视性刺激作用的作用。
Methamphetamine is a psychostimulant drug acting on central monoaminergic neurons to produce both acute psychomotor stimulation and long-lasting behavioral effects including addiction and psychosis. Drug discrimination procedures have been particularly useful in characterizing subjective effects of addictive drugs. In the present study, to identify potential anatomical substrates for the discriminative stimulus effects of methamphetamine, we investigated the drug discrimination-associated Fos expression in Sprague-Dawley rats trained to discriminate methamphetamine from saline under a two-lever fixed ratio 20 (FR-20) schedule of food reinforcement. The rats that fulfilled the criteria for learning the discrimination were anesthetized and perfused 2 h after the drug discrimination test, and Fos immunoreactivity was examined in 15 brain regions. Fos expression in the brains of rats that discriminate methamphetamine from saline was significantly increased in the nucleus accumbens (NAc) and the ventral tegmental area (VTA), but not in other areas including the cerebral cortex, caudate putamen, substantia nigra, hippocampus, amygdala and habenulla, as compared with the expression in control rats that were maintained under the FR-20 schedule. The present findings suggest a role for the VTA and NAc as possible neuronal substrates in the discriminative stimulus effects of methamphetamine.