Mori Tomohisa, Ito Shinobu, Narita Minoru, Suzuki Tsutomu, Sawaguchi Toshiko
Department of Legal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
J Pharmacol Sci. 2004 Dec;96(4):450-8. doi: 10.1254/jphs.fpj04039x. Epub 2004 Dec 10.
Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. This combination appears to produce synergistic effects on behavior at low doses; however, there is little direct evidence that the combination is stronger than either drug alone. Therefore, we investigated interactions between psychostimulants and morphine on locomotor activity in mice. Low doses of cocaine (5.0 mg/kg) or methamphetamine (0.5 mg/kg) and morphine (10 mg/kg) enhance locomotor activity in a synergistic fashion. Effective doses of cocaine (20 mg/kg) and morphine (20 mg/kg) increased locomotion in an additive fashion. In contrast, combination of methamphetamine (1.0 and 2.0 mg/kg) and morphine (10 and 20 mg/kg) did not merely enhance their effects (or attenuated the peak effects of methamphetamine-induced hyperlocomotion). These results indicate that different mechanisms explain the interaction between morphine and methamphetamine or cocaine. It is well known that psychostimulants- and opioids-induced hyperlocomotion is mediated by the activation of the dopaminergic system, however, haloperidol (a dopamine receptor antagonist) and U50,488H (which attenuates dopamine release from nerve terminals) significantly increased the effects of methamphetamine and morphine on the locomotor activity. These results suggest that excess dopaminergic activation may be involved in the effects of methamphetamine and morphine on locomotor activity in mice.
同时使用精神兴奋剂和阿片类药物是全球主要的药物滥用问题。这种组合在低剂量时似乎对行为产生协同作用；然而，几乎没有直接证据表明这种组合比单独使用任何一种药物的效果更强。因此，我们研究了精神兴奋剂和吗啡对小鼠运动活动的相互作用。低剂量的可卡因（5.0毫克/千克）或甲基苯丙胺（0.5毫克/千克）与吗啡（10毫克/千克）以协同方式增强运动活动。有效剂量的可卡因（20毫克/千克）和吗啡（20毫克/千克）以相加方式增加运动。相比之下，甲基苯丙胺（1.0和2.0毫克/千克）与吗啡（10和20毫克/千克）的组合不仅没有增强它们的效果（或减弱甲基苯丙胺诱导的运动亢进的峰值效应）。这些结果表明，不同的机制解释了吗啡与甲基苯丙胺或可卡因之间的相互作用。众所周知，精神兴奋剂和阿片类药物诱导的运动亢进是由多巴胺能系统的激活介导的，然而，氟哌啶醇（一种多巴胺受体拮抗剂）和U50,488H（可减弱神经末梢多巴胺释放）显著增加了甲基苯丙胺和吗啡对运动活动的影响。这些结果表明，多巴胺能过度激活可能参与了甲基苯丙胺和吗啡对小鼠运动活动的影响。
