Narita Minoru, Asato Megumi, Shindo Keiko, Kuzumaki Naoko, Suzuki Tsutomu
Department of Toxicology, Hoshi University School of Pharmacological Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2009 Jun;29(3):115-20.
Methylphenidate (MPH) is commonly used in the treatment of narcolepsy and attention deficit/hyperactivity disorder (AD/HD) in Japan. MPH has been also known to have psychostimulus effects similar to methamphetamine (METH). In the present study, we compared several effects of MPH to METH. It is well-known that the repeated administration of psychostimulant drugs induces behavioral sensitization. However, MPH failed to induce sensitization to hyperlocomotion, while METH clearly induced behavioral sensitization. Moreover, the METH-induced rewarding effect was maintained even 2 weeks after withdrawal of METH. In contrast, the MPH-induced rewarding effect almost disappeared within 2 weeks after withdrawal of MPH. We next investigated the effect of METH and MPH on astrocytes, which have been known to play an important role in neuronal network systems. Both METH and MPH induced astrocytic activation in limbic neuron/glia cocultures. It is of interest to note that the METH-induced astrocytic activation was still present after an additional 2 days of culture with normal medium. Unlike METH, the MPH-induced astrocytic activation was reversed within 2 days after washout of MPH. Furthermore, high concentration of METH, but not MPH, reduced MAP2a/b positive cells and activated the immunoreactivity of the cleaved caspase-3 in primary cultured limbic neurons, whereas MPH had no such effect. Taken together, the present findings suggest that the psychostimulus effects of METH and MPH occur through different mechanisms.
在日本，哌甲酯（MPH）常用于治疗发作性睡病和注意力缺陷多动障碍（AD/HD）。人们还知道MPH具有与甲基苯丙胺（METH）相似的精神刺激作用。在本研究中，我们比较了MPH和METH的几种作用。众所周知，反复给予精神刺激药物会诱发行为敏化。然而，MPH未能诱发对运动亢进的敏化，而METH则明显诱发了行为敏化。此外，即使在停用METH 2周后，METH诱导的奖赏效应仍持续存在。相比之下，MPH诱导的奖赏效应在停用MPH后2周内几乎消失。接下来，我们研究了METH和MPH对星形胶质细胞的影响，已知星形胶质细胞在神经网络系统中起重要作用。METH和MPH均可在边缘神经元/神经胶质细胞共培养物中诱导星形胶质细胞活化。值得注意的是，在用正常培养基再培养2天后，METH诱导的星形胶质细胞活化仍然存在。与METH不同，MPH诱导的星形胶质细胞活化在洗去MPH后2天内逆转。此外，高浓度的METH而非MPH可减少原代培养的边缘神经元中微管相关蛋白2a/b（MAP2a/b）阳性细胞，并激活裂解的半胱天冬酶-3的免疫反应性，而MPH则无此作用。综上所述，目前的研究结果表明，METH和MPH的精神刺激作用通过不同机制发生。
