Ginawi O T, Al-Majed A A, Al-Suwailem A K, El-Hadiyah T M H
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
J Physiol Pharmacol. 2004 Jun;55(2):357-69.
Effects of some selective 5-HT antagonists on methamphetamine-induced locomotor activity were investigated in male mice in order to study whether this effect of methamphetamine is selectively or at least partially, induced through stimulation of a specific serotonin receptor subtype. Methamphetamine (1.5 mg/kg, IP) produced a significant increase in locomotor activity. Methamphetamine-induced hyperactivity by the above mentioned dose was significantly antagonized by NAN-190 ( 5-HT(1A) antagonist) at a dose of 4 mg/kg, IP, methiothepin (5-HT(1B/1D) antagonist) at a dose of 0.1mg/kg, IP or mianserin ( 5-HT(2C) antagonist) at a dose of 8 mg/kg, IP. On the other hand, methysergide ( 5-HT(2A/2B) antagonist) at a dose of 1mg/kg, IP or ondansetron ( 5-HT(3) antagonist) at a dose of 0.5mg/kg, IP potentiated the methamphetamine-induced hyperactivity. None of the above mentioned doses of 5-HT antagonists altered the spontaneous activity of mice when administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the locomotor stimulant activity of methamphetamine in mice. This role is possibly mediated through direct stimulation of some 5-HT receptor subtypes. Stimulation by methamphetamine of 5-HT(1A), 5-HT(1B/1D) and/or 5-HT(2C) receptor subtypes may result in hyperactivity, whereas stimulation by methamphetamine of 5-HT(2A/2B) and/or 5-HT(3) receptor subtypes may result in decreased activity.
为了研究甲基苯丙胺的这种作用是否是通过刺激特定的5-羟色胺受体亚型选择性地或至少部分地诱导产生的，我们在雄性小鼠中研究了一些选择性5-羟色胺拮抗剂对甲基苯丙胺诱导的运动活性的影响。甲基苯丙胺（1.5毫克/千克，腹腔注射）使运动活性显著增加。上述剂量的甲基苯丙胺诱导的多动被腹腔注射4毫克/千克的NAN-190（5-羟色胺（1A）拮抗剂）、0.1毫克/千克的甲硫噻平（5-羟色胺（1B/1D）拮抗剂）或8毫克/千克的米安色林（5-羟色胺（2C）拮抗剂）显著拮抗。另一方面，腹腔注射1毫克/千克的麦角新碱（5-羟色胺（2A/2B）拮抗剂）或0.5毫克/千克的昂丹司琼（5-羟色胺（3）拮抗剂）增强了甲基苯丙胺诱导的多动。上述剂量的5-羟色胺拮抗剂单独给药时均未改变小鼠的自发活动。本研究结果表明，除了儿茶酚胺能系统外，5-羟色胺能机制在小鼠甲基苯丙胺的运动兴奋活性中可能起作用。这种作用可能是通过直接刺激某些5-羟色胺受体亚型介导的。甲基苯丙胺对5-羟色胺（1A）、5-羟色胺（1B/1D）和/或5-羟色胺（2C）受体亚型的刺激可能导致多动，而甲基苯丙胺对5-羟色胺（2A/2B）和/或5-羟色胺（3）受体亚型的刺激可能导致活动减少。
