Suzuki Tsutomu, Shindo Keiko, Miyatake Mayumi, Kurokawa Kazuhiro, Higashiyama Kimio, Suzuki Masami, Narita Minoru
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan.
Eur J Pharmacol. 2007 Nov 21;574(1):39-48. doi: 10.1016/j.ejphar.2007.06.062. Epub 2007 Jul 13.
Methamphetamine is a powerfully addictive psychostimulant that dramatically affects the mammalian central nervous system. Methylphenidate has been shown to have psychostimulus effects similar to methamphetamine. In the present study, we compared several effects of methylphenidate to those of methamphetamine. The subcutaneous administration of either methamphetamine or methylphenidate increased extracellular dopamine levels in the nucleus accumbens of mice. Interestingly, methamphetamine, but not methylphenidate, also increased the extracellular serotonin levels in this area. Further, repeated treatment with methamphetamine induced the development of sensitization to hyperlocomotion, whereas methylphenidate failed to induce behavioral sensitization. Moreover, in vitro treatment with methamphetamine, but not methylphenidate, caused long-lasting astrocytic activation in limbic neuron/glia co-cultures. These findings suggest that, unlike methamphetamine, methylphenidate shows a lack of development of behavioral sensitization to its hyperlocomotion and induces reversible astrocytic activation.
甲基苯丙胺是一种极易成瘾的精神兴奋剂，会对哺乳动物中枢神经系统产生显著影响。已证明哌甲酯具有与甲基苯丙胺相似的精神刺激作用。在本研究中，我们比较了哌甲酯与甲基苯丙胺的几种作用。皮下注射甲基苯丙胺或哌甲酯均可增加小鼠伏隔核细胞外多巴胺水平。有趣的是，甲基苯丙胺而非哌甲酯还会增加该区域细胞外血清素水平。此外，重复给予甲基苯丙胺会导致对运动亢进的敏化作用产生，而哌甲酯未能诱导行为敏化。而且，在体外培养中，甲基苯丙胺而非哌甲酯会在边缘神经元/神经胶质细胞共培养物中引起持久的星形胶质细胞活化。这些发现表明，与甲基苯丙胺不同，哌甲酯对其运动亢进未表现出行为敏化的发展，且诱导的是可逆的星形胶质细胞活化。
