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单胺氧化酶抑制剂对小鼠和大鼠甲基苯丙胺诱导的刻板行为的影响。

Effects of monoamine oxidase inhibitors on methamphetamine-induced stereotypy in mice and rats.

作者信息

Tatsuta Tomohiro, Kitanaka Nobue, Kitanaka Junichi, Morita Yoshio, Takemura Motohiko

机构信息

Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Hyogo, Japan.

出版信息

Neurochem Res. 2005 Nov;30(11):1377-85. doi: 10.1007/s11064-005-8390-2.

Abstract

In male ICR mice, a single intraperitoneal administration of methamphetamine (METH) (10 mg/kg) induced stereotyped behavior such as continuous sniffing, circling, and nail biting, reaching a plateau level 20 min after the injection. Subcutaneous pretreatment with clorgyline, a monoamine oxidase (MAO)-A inhibitor, at a dose of 0.1 mg/kg 2 h prior to the drug challenge significantly decreased the initial (first 20 min) intensity of stereotypies and increased the latency to onset. The effect was not observed with either higher doses of clorgyline (1 and 10 mg/kg) or l-deprenyl, a MAO-B inhibitor, at doses of 0.1-10 mg/kg. In male Wistar rats, the inhibitory effect of clorgyline on METH-induced stereotypy was not observed. Pretreatment of the mice with clorgyline (0.1 mg/kg) had no effect on apparent serotonin and dopamine turnover in the striatum, although the higher doses of clorgyline (1 and 10 mg/kg) significantly decreased the turnover. These results suggest that a low dose of clorgyline tends to increase the latency and decrease the intensity of stereotypies induced by METH in a dopamine metabolism-independent manner in mice.

摘要

在雄性ICR小鼠中,单次腹腔注射甲基苯丙胺(METH)(10毫克/千克)会诱发刻板行为,如持续嗅探、转圈和咬指甲,注射后20分钟达到平稳水平。在药物激发前2小时,以0.1毫克/千克的剂量皮下注射氯吉兰(一种单胺氧化酶(MAO)-A抑制剂),可显著降低刻板行为最初20分钟的强度,并延长发作潜伏期。更高剂量的氯吉兰(1和10毫克/千克)或MAO-B抑制剂l-司来吉兰(剂量为0.1 - 10毫克/千克)均未观察到这种效果。在雄性Wistar大鼠中,未观察到氯吉兰对METH诱导的刻板行为有抑制作用。用氯吉兰(0.1毫克/千克)预处理小鼠对纹状体中血清素和多巴胺的明显周转率没有影响,尽管更高剂量的氯吉兰(1和10毫克/千克)显著降低了周转率。这些结果表明,低剂量的氯吉兰倾向于以与多巴胺代谢无关的方式增加小鼠中METH诱导的刻板行为的潜伏期并降低其强度。

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