Imaki Junta, Mae Yukari, Shimizu Saki, Ohno Yukihiro
Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Neurosci Lett. 2009 Apr 24;454(2):143-7. doi: 10.1016/j.neulet.2009.03.001. Epub 2009 Mar 5.
We examined the effects of JP-1302 (a selective alpha2C antagonist), BRL-44408 (a selective alpha2A antagonist) and yohimbine (a non-selective alpha2 antagonist) on haloperidol-induced bradykinesia and catalepsy in mice to elucidate the role of alpha2 adrenoceptor subtypes in modifying extrapyramidal motor disorders. JP-1302 (0.1-1 mg/kg, s.c.) dose-dependently ameliorated haloperidol-induced bradykinesia in the pole-test and reversed the catalepsy time increased by haloperidol. Antibradykinetic and anticataleptic actions of JP-1302 were statistically significant at 0.3 and 1 mg/kg, and these doses did not alter the ambulatory distance, rearing or center-perimeter residence time in the open-field test. BRL-44408 (1-10 mg/kg, s.c.) and yohimbine (0.3-3 mg/kg, i.p.) also ameliorated haloperidol-induced bradykinesia and catalepsy. However, both agents significantly decreased ambulatory distance and rearing in the open-field test, possibly reflecting their anxiogenic actions associated with alpha2A antagonism. The present study shows for the first time that blockade of alpha2C receptors can alleviate antipsychotic-induced extrapyramidal motor disorders without affecting gross behaviors.
我们研究了 JP - 1302（一种选择性α2C拮抗剂）、BRL - 44408（一种选择性α2A拮抗剂）和育亨宾（一种非选择性α2拮抗剂）对氟哌啶醇诱导的小鼠运动迟缓及僵住症的影响，以阐明α2肾上腺素能受体亚型在改善锥体外系运动障碍中的作用。JP - 1302（0.1 - 1毫克/千克，皮下注射）剂量依赖性地改善了氟哌啶醇在攀杆试验中诱导的运动迟缓，并逆转了氟哌啶醇增加的僵住症时间。JP - 1302的抗运动迟缓及抗僵住症作用在0.3和1毫克/千克时具有统计学意义，且这些剂量在旷场试验中未改变行走距离、竖毛或中央 - 周边停留时间。BRL - 44408（1 - 10毫克/千克，皮下注射）和育亨宾（0.3 - 3毫克/千克，腹腔注射）也改善了氟哌啶醇诱导的运动迟缓及僵住症。然而，这两种药物在旷场试验中均显著降低了行走距离和竖毛行为，这可能反映了它们与α2A拮抗作用相关的致焦虑作用。本研究首次表明，阻断α2C受体可减轻抗精神病药物诱导的锥体外系运动障碍，而不影响总体行为。
