National Institute on Drug Dependence, Peking University, B38 Xue Yuan Road, Haidian, Beijing, China.
Int J Neuropsychopharmacol. 2013 Sep;16(8):1767-80. doi: 10.1017/S1461145713000072. Epub 2013 Mar 1.
Melanin-concentrating hormone (MCH) is a neuropeptide and its receptor is extensively expressed throughout the brain. MCH has been suggested to regulate the rewarding and reinforcing effects of psychostimulants by potentiating the dopaminergic system within the midbrain. Moreover, MCH and its receptor can regulate ERK activity. The present study investigated the role of MCH in the nucleus accumbens (NAc) in rats behaviourally sensitized to methamphetamine (Meth). We found that the development of Meth-induced locomotor sensitization was attenuated by MCH infused into the NAc shell but not core. Moreover, the elevation of ERK phosphorylation in the NAc shell induced by Meth was inhibited by locally infused MCH. Infusion of the MCH receptor 1 (MCHR1) antagonist SNAP 94847 into the NAc shell but not core augmented the initiation of locomotor sensitization and amplitude of elevated phosphorylated ERK levels induced by Meth. The expression of Meth-induced locomotor sensitization and ERK alterations after 1 wk withdrawal were not affected by either MCH or SNAP 94847 infused into the NAc shell or core. These results indicate that MCH in the NAc shell plays a critical role in the development but not expression of Meth-induced locomotor sensitization in rats, which might be mediated by the ERK signalling pathway. Our study suggests that MCH might be a potential target for the treatment of Meth addiction.
黑色素浓缩激素 (MCH) 是一种神经肽，其受体广泛表达于整个大脑中。MCH 被认为通过增强中脑内的多巴胺能系统来调节精神兴奋剂的奖赏和强化作用。此外，MCH 和其受体可以调节 ERK 活性。本研究探讨了 MCH 在对甲基苯丙胺 (Meth) 行为敏感化的大鼠伏隔核 (NAc) 中的作用。我们发现，MCH 注入 NAc 壳而不是核，可减弱 Meth 诱导的运动敏化的发展。此外，Meth 诱导的 NAc 壳中 ERK 磷酸化的升高被局部注入的 MCH 抑制。将 MCH 受体 1 (MCHR1) 拮抗剂 SNAP 94847 注入 NAc 壳而不是核，可增强 Meth 诱导的运动敏化的起始和升高的磷酸化 ERK 水平的幅度。MCH 或 SNAP 94847 注入 NAc 壳或核，对 1 周戒断后 Meth 诱导的运动敏化和 ERK 改变的表达均无影响。这些结果表明，NAc 壳中的 MCH 在大鼠 Meth 诱导的运动敏化的发展中起着关键作用，但在表达中不起作用，这可能是通过 ERK 信号通路介导的。我们的研究表明，MCH 可能是治疗 Meth 成瘾的潜在靶点。
