Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine
Implication of brain-derived neurotrophic factor in the release of dopamine and dopamine-related behaviors induced by methamphetamine
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DOI：
10.1016/s0306-4522(03)00099-x
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Narita, M;Aoki, K;Suzuki, T
人们普遍认为，甲基苯丙胺可以增强中脑边缘系统多巴胺能神经元末端多巴胺的释放，从而诱导多巴胺相关行为。脑源性神经营养因子（BDNF）是一种神经营养因子，与酪氨酸激酶特异性受体TrkB结合并激活。BDNF已被证明可以影响中脑边缘多巴胺系统中多巴胺的释放。本研究旨在探讨BDNF和TrkB在大鼠甲基苯丙胺诱导的伏隔核多巴胺释放表达和甲基苯丙胺诱导的多巴胺相关行为中的作用。甲基苯丙胺（1 mg/kg, s.c）使细胞外多巴胺水平显著增加，并诱导多巴胺相关行为（如饲养和嗅探）逐渐增强。相比之下，在伏隔核内注射BDNF （2.0 mul/大鼠，1:1000,1:30 00和1:1000）或TrkB （2.0 mul/大鼠，1:1000和1:1000）抗体预处理后，甲基苯丙胺对多巴胺释放的刺激和多巴胺相关行为的诱导均被显著抑制。此外，伏隔核多巴胺的基础水平不受BDNF和TrkB抗体治疗的影响。这些发现进一步证明BDNF/TrkB通路与甲基苯丙胺诱导的多巴胺释放和多巴胺相关行为的诱导有关。(c) 2003年。Elsevier Science Ltd.出版。版权所有。
It is widely recognized that methamphetamine enhances the release of dopamine at dopaminergic neuron terminals of the mesolimbic system, which induces dopamine-related behaviors. Brain-derived neurotrophic factor (BDNF), a neurotrophin, binds to and activates its specific receptor tyrosine kinase, TrkB. BDNF has been shown to influence the release of dopamine in the mesolimbic dopamine system. The present study was designed to investigate roles of BDNF and TrkB in the expression of methamphetamine-induced dopamine release in the nucleus accumbens and dopamine-related behaviors induced by methamphetamine in rats. Methamphetamine (1 mg/kg, s.c.) produced a substantial increase in the extracellular levels of dopamine and induced a progressive augmentation of dopamine-related behaviors such as rearing and sniffing. In contrast, both the stimulation of dopamine release and induction of dopamine-related behaviors by methamphetamine were significantly suppressed by pretreatment with intra-nucleus accumbens injection of either BDNF (2.0 mul/rat, 1:1000, 1:300 and 1:100) or TrkB (2.0 mul/rat, 1:1000 and 1:100) antibody. Furthermore, the basal level of dopamine in the nucleus accumbens was not affected by treatment with both BDNF and TrkB antibodies. These findings provide further evidence that BDNF/TrkB pathway is implicated in the methamphetamine-induced release of dopamine and the induction of dopamine-related behaviors. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.