Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine
Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine
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DOI：
10.1016/s0024-3205(00)00995-4
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发表时间：
2001-01-19
期刊：
影响因子：
6.1
通讯作者：
Chiang, YC
中科院分区：
文献类型：
--
作者：
Chen, JC;Liang, KW;Chiang, YC
为了探讨腹侧苍白球（VP）在苯丙胺致敏过程中的意义，我们首先研究了VP在苯丙胺戒断期是否有神经化学变化。在停药第10 - 14天用2 mg/kg安非他明激发时，与生理盐水对照组相比，慢性安非他明给药（5 mg/kg × 14天）大鼠显示出明显的运动致敏性。微透析分析表明，输出的多巴胺代谢产物，3，4-二羟基苯乙酸和高香草酸，在安非他明致敏大鼠VP增加约2倍，与对照组相比，在前和后安非他明的挑战期。另一方面，在VP的体内谷氨酸输出增加安非他明的挑战后，在行为致敏大鼠，但不是在控制。为了评估VP中的药物操作是否会影响行为敏化，我们在停药第6 - 10天期间在VP中用NMDA受体拮抗剂MK-801（5 μ g/μ l，持续5天;双侧）处理两组大鼠。在停药第11天，用2 mg/kg安非他明激发动物。行为学特征显示MK-801预处理显著阻断苯丙胺致敏大鼠的运动过度活动。两者合计，目前的结果表明，兴奋性氨基酸在VP中起着显着的作用，在表达的行为敏化安非他明。(C)2001 Elsevier Science Inc. All rights reserved.
To explore the significance of ventral pallidum (VP) during the amphetamine sensitization, we first investigated if there are neurochemical alterations in the VP during amphetamine withdrawal period. Chronic amphetamine-treated (5 mg/kg X 14 days) rats displayed an apparent locomotion sensitization as compared with saline controls when challenged with 2 mg/kg amphetamine at withdrawal days 10-14. A rnicrodialysis analysis revealed that output of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the VP of amphetamine-sensitized rats increased approximately two-fold as compared to controls at both pre- and post-amphetamine challenge period. On the other hand, the in vivo glutamate output in the VP increased upon amphetamine challenge in the behaviorally sensitized rats, but not in the controls. To evaluate if drug manipulation in the VP would affect the behavioral sensitization, we treated both groups of rats with NMDA receptor antagonist, MK-801 (5 mug/mul for 5 days; bilateral) in the VP during withdrawal days 6-10. Animals were challenged with 2 mg/kg amphetamine at withdrawal day 11. The behavioral profile exhibited that MK-801 pre-treatment significantly blocked the locomotion hyperactivity in amphetamine-sensitized rats. Taken together, the current results suggest that the excitatory amino acid in the VP plays a significant role during the expression of behavioral sensitization to amphetamine. (C) 2001 Elsevier Science Inc. All rights reserved.