Narita M, Aoki K, Takagi M, Yajima Y, Suzuki T
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan.
Neuroscience. 2003;119(3):767-75. doi: 10.1016/s0306-4522(03)00099-x.
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 microl/rat, 1:1000, 1:300 and 1:100) or TrkB (2.0 microl/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.
人们普遍认为，甲基苯丙胺会增强中脑边缘系统多巴胺能神经元终末的多巴胺释放，从而诱发与多巴胺相关的行为。脑源性神经营养因子（BDNF）作为一种神经营养蛋白，能与其特异性受体酪氨酸激酶TrkB结合并激活它。已有研究表明，BDNF会影响中脑边缘多巴胺系统中多巴胺的释放。本研究旨在探究BDNF和TrkB在甲基苯丙胺诱导的大鼠伏隔核多巴胺释放及甲基苯丙胺诱导的与多巴胺相关行为的表达中所起的作用。甲基苯丙胺（1毫克/千克，皮下注射）使细胞外多巴胺水平大幅升高，并使诸如竖毛和嗅探等与多巴胺相关的行为逐渐增加。相比之下，通过伏隔核内注射BDNF（2.0微升/只大鼠，1:1000、1:300和1:100）或TrkB（2.0微升/只大鼠，1:1000和1:100）抗体进行预处理，可显著抑制甲基苯丙胺对多巴胺释放的刺激以及对与多巴胺相关行为的诱导。此外，BDNF和TrkB抗体处理均未影响伏隔核中多巴胺的基础水平。这些发现进一步证明，BDNF/TrkB信号通路与甲基苯丙胺诱导的多巴胺释放及与多巴胺相关行为的诱导有关。
