Kitanaka Nobue, Kitanaka Junichi, Hall F Scott, Kayama Masaru, Sugimori Hironobu, Uhl George R, Takemura Motohiko
Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA.
J Exp Neurosci. 2015 Sep 10;9(Suppl 1):1-10. doi: 10.4137/JEN.S27733. eCollection 2015.
Aripiprazole is a third-generation atypical antipsychotic and a dopamine D2 receptor partial agonist. In the present study, we investigated whether a single administration of aripiprazole to mice, either as a pretreatment or as a posttreatment, would affect stereotypy induced by methamphetamine (METH). Pretreatment of male ICR mice with aripiprazole (1 or 10 mg/kg, i.p.) attenuated the incidence of METH-induced stereotypical behavior in a dose-dependent manner. Pretreatment of mice with 1 mg/kg aripiprazole produced an increase in the locomotor activity in mice treated with METH compared with mice treated with vehicle plus METH and with 10 mg/kg aripiprazole plus METH. This increase in locomotion is indicative of a rightward shift in the dose-response curve for METH, consistent with a shift in the type of stereotypical behavior observed from biting to sniffing. Aripiprazole posttreatment, after METH-induced stereotypical behavior, was fully expressed and also significantly attenuated overall stereotypy in an aripiprazole dose-dependent manner. These data suggest that the antagonism of METH effects by aripiprazole should be investigated as a potential treatment for acute METH overdose.
阿立哌唑是一种第三代非典型抗精神病药物，也是一种多巴胺D2受体部分激动剂。在本研究中，我们调查了对小鼠单次给予阿立哌唑（无论是预处理还是后处理）是否会影响甲基苯丙胺（METH）诱导的刻板行为。用阿立哌唑（1或10mg/kg，腹腔注射）对雄性ICR小鼠进行预处理，可剂量依赖性地减轻METH诱导的刻板行为的发生率。与用赋形剂加METH以及10mg/kg阿立哌唑加METH处理的小鼠相比，用1mg/kg阿立哌唑预处理的小鼠在用METH处理后其运动活性增加。这种运动增加表明METH剂量-反应曲线向右移动，这与观察到的刻板行为类型从咬转为嗅的转变一致。在METH诱导的刻板行为出现后进行阿立哌唑后处理，可完全表达且也能以阿立哌唑剂量依赖性方式显著减轻总体刻板行为。这些数据表明，应研究阿立哌唑对METH效应的拮抗作用，作为急性METH过量的一种潜在治疗方法。
