Tatsuta Tomohiro, Kitanaka Nobue, Kitanaka Junichi, Morita Yoshio, Takemura Motohiko
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Pharmacol Biochem Behav. 2007 May;87(1):48-55. doi: 10.1016/j.pbb.2007.03.019. Epub 2007 Apr 6.
The effects of topiramate, a structurally novel anticonvulsant, on the methamphetamine (METH)-induced expression of stereotypy and conditioned place preference (CPP) in male ICR mice were investigated. After a single administration of METH (10 mg/kg, i.p.), mice showed stereotyped behaviors with a plateau level 25 min after drug challenge. Pretreatment with topiramate (1, 10, and 100 mg/kg, i.p.) 30 min prior to METH challenge had no effect on the expression frequency of stereotypy, compared with saline challenge. No differential effects of topiramate on METH-induced stereotyped behavior (that is, head-bobbing, circling, continuous sniffing, nail and/or wood-chip biting, and vigorous and compulsive grooming) were observed. In saline-challenged groups, the doses of topiramate examined did not induce any stereotyped behaviors. Although mice showed a significant CPP for METH (0.5 mg/kg, i.p.), pretreatment with subchronic topiramate did not affect the magnitude of CPP. Locomotor activity was not affected by the doses of topiramate tested. Conditioned rewarding or aversive effects of topiramate were not observed as indexed by the place preference procedure. These results suggested the lack of effect of topiramate on METH-induced stereotypy and rewarding property in mice.
研究了结构新颖的抗惊厥药物托吡酯对雄性ICR小鼠甲基苯丙胺(METH)诱导的刻板行为表达和条件性位置偏爱(CPP)的影响。单次腹腔注射METH(10 mg/kg)后,小鼠在药物激发后25分钟出现刻板行为且达到稳定水平。与生理盐水激发组相比,在METH激发前30分钟腹腔注射托吡酯(1、10和100 mg/kg)对刻板行为的表达频率没有影响。未观察到托吡酯对METH诱导的刻板行为(即点头、转圈、持续嗅探、咬指甲和/或木屑、剧烈且强迫性梳理毛发)有差异效应。在生理盐水激发组中,所检测的托吡酯剂量未诱发任何刻板行为。尽管小鼠对腹腔注射0.5 mg/kg的METH表现出显著的CPP,但亚慢性托吡酯预处理并未影响CPP的程度。所测试的托吡酯剂量对运动活性没有影响。通过位置偏爱程序未观察到托吡酯的条件性奖赏或厌恶效应。这些结果表明托吡酯对小鼠METH诱导的刻板行为和奖赏特性没有影响。