Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.).
Department of Toxicology (T.M., N.U., H.K., H.W., A.M., M.S., T.S.) and Institute of Medicinal Chemistry (K.H.), Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan; and Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Tokyo, Japan (K.Y.)
J Pharmacol Exp Ther. 2014 Aug;350(2):403-11. doi: 10.1124/jpet.114.214288. Epub 2014 Jun 10.
Previous studies have demonstrated that methylphenidate, MDMA (3,4-methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like subjective effects in humans. Furthermore, MDMA and methylphenidate substitute for the discriminative stimulus effects of psychostimulants, such as amphetamine and cocaine, in animals, which suggests that MDMA and methylphenidate may produce similar discriminative stimulus effects in rats. However, there is no evidence regarding the similarities between the discriminative stimulus effects of MDMA and methylphenidate. To explore this issue, cross-substitution, substitution, and combination tests were conducted in rats that had been trained to discriminate between MDMA (2.5 mg/kg) or methylphenidate (5.0 mg/kg) and saline. In the cross-substitution tests, MDMA and methylphenidate did not cross-substitute for each other. In the substitution test, methamphetamine substituted for the discriminative stimulus effects of methylphenidate, but not for those of MDMA. Furthermore, ephedrine and bupropion, which activate dopaminergic and noradrenergic systems, substituted for the discriminative stimulus effects of methylphenidate. On the other hand, serotonin (5-HT) receptor agonists 5-HT1A and 5-HT2 fully substituted for the discriminative stimulus effects of MDMA. These results suggest that activation of the noradrenergic and dopaminergic systems is important for the discriminative stimulus effects of methylphenidate, whereas activation of the serotonergic system is crucial for the discriminative stimulus effects of MDMA. Even though MDMA, like psychostimulants, exerts stimulant-like effects, our findings clearly indicate that the discriminative stimulus effects of MDMA are distinctly different from those of other psychostimulants in rats.
先前的研究已经表明，哌醋甲酯、MDMA（3,4-亚甲基二氧甲基苯丙胺）和其他兴奋剂在人类中产生兴奋剂样的主观效应。此外，MDMA 和哌醋甲酯在动物中替代了兴奋剂如安非他命和可卡因的辨别刺激效应，这表明 MDMA 和哌醋甲酯可能在大鼠中产生类似的辨别刺激效应。然而，关于 MDMA 和哌醋甲酯的辨别刺激效应之间的相似性，尚无证据。为了探讨这个问题，在已经训练大鼠辨别 MDMA（2.5 毫克/公斤）或哌醋甲酯（5.0 毫克/公斤）和盐水的基础上，进行了交叉替代、替代和组合测试。在交叉替代测试中，MDMA 和哌醋甲酯彼此不能交叉替代。在替代测试中，甲基苯丙胺替代了哌醋甲酯的辨别刺激效应，但不能替代 MDMA 的辨别刺激效应。此外，激活多巴胺能和去甲肾上腺素能系统的麻黄碱和安非他酮替代了哌醋甲酯的辨别刺激效应。另一方面，5-HT1A 和 5-HT2 等 5-HT 受体激动剂完全替代了 MDMA 的辨别刺激效应。这些结果表明，去甲肾上腺素能和多巴胺能系统的激活对哌醋甲酯的辨别刺激效应很重要，而 5-HT 能系统的激活对 MDMA 的辨别刺激效应至关重要。尽管 MDMA 与兴奋剂一样具有兴奋剂样作用，但我们的研究结果清楚地表明，MDMA 的辨别刺激效应在大鼠中与其他兴奋剂明显不同。
