Repeated administration of methamphetamine causes hypersensitivity of D2 receptor in rat ventral tegmental area
Repeated administration of methamphetamine causes hypersensitivity of D2 receptor in rat ventral tegmental area
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DOI：
10.1016/s0304-3940(03)00673-6
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发表时间：
2003-08-21
影响因子：
2.5
通讯作者：
Sakai, N
中科院分区：
文献类型：
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作者：
Amano, T;Matsubayashi, H;Sakai, N
为了阐明甲基苯丙胺（MAP）诱导的多巴胺超敏反应是否发生在腹侧被盖区（VTA），膜片钳研究使用脑片制备。8-10日龄大鼠每天给予MAP或生理盐水，持续5天。第5天，对经形态学和电生理学鉴定的腹侧被盖区多巴胺神经元进行膜片钳研究。多巴胺（1 - 100 μ M）和他立泊索（多巴胺D2受体激动剂，1 - 100 μ M）在这些神经元中产生剂量依赖性超极化; SKF 38393或PD 128907（分别为D1和D3受体激动剂）治疗没有影响。MAP组的超极化程度显著高于生理盐水对照组，表明重复MAP给药导致对多巴胺的超敏反应，这是D2受体依赖性的。这种超敏反应降低了腹侧被盖区多巴胺神经元的兴奋性，从而减少了伏隔核区域的多巴胺释放。这可能会补偿MAP诱导的多巴胺水平升高，并调节多巴胺诱导的信号转导级联，导致背侧核神经元的逆转耐受。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
To elucidate whether the methamphetamine (MAP)-induced hypersensitivity to dopamine occurs in the ventral tegmental area (VTA), patch clamp studies were performed using brain slice preparations. MAP or physiological saline was administered to 8-10-day-old rats daily for 5 days. On day 5, patch clamp studies were performed on VTA dopamine neurons which were identified by morphological and electrophysiological characteristics. Dopamine (1 - 100 muM) and talipexole (a dopamine D2 receptor agonist, 1 - 100 muM) produced a dose-dependent hyperpolarization in these neurons; treatment with SKF 38393 or PD 128907 (D1 and D3 receptor agonists, respectively) had no effect. The extent of hyperpolarization was significantly greater in the MAP group compared to the saline controls, suggesting that repeated MAP administration causes a hypersensitivity to dopamine that is D2 receptor-dependent. This hypersensitivity reduces the excitability of VTA dopamine neurons, thus decreasing dopamine release in the nucleus accumbens area. This may compensate for the MAP-induced elevation of dopamine levels and modulate the dopamine-induced signal transduction cascades, leading to reverse tolerance in nucleus accumbens neurons. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.