Kobayashi T, Araki T, Itoyama Y, Takeshita M, Ohta T, Oshima Y
Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Life Sci. 1997;61(26):2529-38. doi: 10.1016/s0024-3205(97)01007-2.
L-3,4-Dihydroxyphenylalanine (L-DOPA), the precursor of dopamine, and bromocriptine, a dopamine D2 receptor agonist, were investigated in haloperidol-induced motor impairments in mice using both catalepsy and pole tests. In catalepsy test, subcutaneous treatment with haloperidol (0.125, 0.25 and 0.5 mg/kg) caused a cataleptic effect in mice in a dose-dependent manner. This cataleptic effect was evident upto 7 hr after haloperidol treatment. In pole test, haloperidol (0.125, 0.25 and 0.5 mg/kg) produced the prolongation of Tturn and TLA as a marker of bradykinesia in mice and the prolongation lasted at least 7 hr after haloperidol treatment. Intraperitoneal co-pretreatment with L-DOPA (400 mg/kg) + carbidopa (10 mg/kg) in mice decreased the catalepsy induced by haloperidol at a dose of 0.125 mg/kg, while co-pretreatment with L-DOPA (200 and 400 mg/kg) + carbidopa (10 mg/kg) dose-dependently decreased the haloperidol (0.125 mg/kg)-induced bradykinesia. The effect of LDOPA + carbidopa in pole test was more pronounced than that in catalepsy test. Intraperitoneal pretreatment with bromocriptine (2 and 4 mg/kg) in mice reduced the catalepsy and bradykinesia produced by haloperidol at a dose of 0.125 mg/kg. The effect of bromocriptine in pole test was relatively similar to that in catalepsy test. Also, co-pretreatment with LDOPA (400 mg/kg) + carbidopa (10 mg/kg) and pretreatment with bromocriptine (2 and 4 mg/kg) significantly decreased the catalepsy induced by haloperidol at a higher dose of 0.5 mg/kg. These results indicate that co-administration with L-DOPA + carbidopa and single treatment with bromocriptine can decrease haloperidol-induced catalepsy and bradykinesia in mice. Furthermore, our study suggests that pole test as well as catalepsy test is of value in the screening of drugs against neuroleptic-induced motor deficits.
使用僵住症和爬杆试验，对L-3,4-二羟基苯丙氨酸（L-DOPA，多巴胺的前体）和溴隐亭（一种多巴胺D2受体激动剂）在氟哌啶醇诱导的小鼠运动障碍中的作用进行了研究。在僵住症试验中，皮下注射氟哌啶醇（0.125、0.25和0.5 mg/kg）以剂量依赖的方式使小鼠产生僵住效应。这种僵住效应在氟哌啶醇治疗后长达7小时都很明显。在爬杆试验中，氟哌啶醇（0.125、0.25和0.5 mg/kg）使小鼠的转身时间（Tturn）和总运动时间（TLA）延长，作为运动迟缓的指标，且这种延长在氟哌啶醇治疗后至少持续7小时。小鼠腹腔内联合预处理L-DOPA（400 mg/kg）+卡比多巴（10 mg/kg）可降低0.125 mg/kg剂量的氟哌啶醇诱导的僵住症，而联合预处理L-DOPA（200和400 mg/kg）+卡比多巴（10 mg/kg）可剂量依赖性地降低氟哌啶醇（0.125 mg/kg）诱导的运动迟缓。L-DOPA +卡比多巴在爬杆试验中的作用比在僵住症试验中更明显。小鼠腹腔内预处理溴隐亭（2和4 mg/kg）可降低0.125 mg/kg剂量的氟哌啶醇产生的僵住症和运动迟缓。溴隐亭在爬杆试验中的作用与在僵住症试验中相对相似。此外，联合预处理L-DOPA（400 mg/kg）+卡比多巴（10 mg/kg）和预处理溴隐亭（2和4 mg/kg）可显著降低0.5 mg/kg较高剂量的氟哌啶醇诱导的僵住症。这些结果表明，联合使用L-DOPA +卡比多巴和单独使用溴隐亭可降低氟哌啶醇诱导的小鼠僵住症和运动迟缓。此外，我们的研究表明，爬杆试验以及僵住症试验在筛选抗精神分裂症药物引起的运动缺陷的药物方面具有价值。
