Kaneko M, Sato K, Horikoshi R, Yaginuma M, Yaginuma N, Shiragata M, Kumashiro H
Department of Neuropsychiatry, Fukushima Medical College, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1992 May;46(1):53-7. doi: 10.1016/0952-3278(92)90059-r.
To investigate the effect of haloperidol (HAL) on second messengers in the brain striatum, the concentrations of cAMP and inositol trisphosphate (IP-3) were measured in the striatum of rats in vivo after intravenous administration of HAL, and their concentrations were compared with the severity of catalepsy and changes in dopamine (DA) metabolism in the striatum. Catalepsy developed both in the animals treated with 5 mg/kg and those with 0.5 mg/kg of HAL, but it appeared earlier, and the period of severe catalepsy was longer in the former than in the latter. In the animals treated with 5 mg/kg of HAL, DOPAC and HVA began to increase at 20 min after administration, and their percent increases were correlated with the severity of catalepsy. In the 5 mg/kg animals, both cAMP and IP-3 increased. The IP-3 showed a delayed peak but a greater increase as compared with the cAMP. In the 0.5 mg/kg animals, only IP-3 increased. These findings suggest that HAL might affect not only the adenylate cyclase system but also the phosphoinositide response in the striatum. Moreover, the changes in the phosphoinositide response might be secondarily induced by the blocking of D-2 receptors by HAL.
为研究氟哌啶醇（HAL）对脑纹状体中第二信使的影响，在大鼠静脉注射HAL后，测定其纹状体中cAMP和肌醇三磷酸（IP - 3）的浓度，并将其浓度与僵住症的严重程度以及纹状体中多巴胺（DA）代谢的变化进行比较。给予5mg/kg和0.5mg/kg HAL的动物均出现了僵住症，但前者出现得更早，且严重僵住症的持续时间比后者更长。在给予5mg/kg HAL的动物中，给药后20分钟DOPAC和HVA开始升高，其升高百分比与僵住症的严重程度相关。在给予5mg/kg HAL的动物中，cAMP和IP - 3均升高。IP - 3出现延迟峰值，但与cAMP相比升高幅度更大。在给予0.5mg/kg HAL的动物中，只有IP - 3升高。这些发现表明，HAL可能不仅影响腺苷酸环化酶系统，还影响纹状体中的磷酸肌醇反应。此外，磷酸肌醇反应的变化可能是由HAL阻断D - 2受体继发诱导的。
