Nabeshima T, Yamaguchi K, Yoshida S, Furukawa H, Kameyama T
Pharmacol Biochem Behav. 1986 May;24(5):1275-9. doi: 10.1016/0091-3057(86)90184-x.
This study was designed to assess the involvement of serotonergic neurons in phencyclidine (PCP)-induced wet-dog shakes in rats after termination of reserpine treatment. Administration of L-5-hydroxytryptophan (7.5-12.5 mg/kg) to rats 30 min following pretreatment with pargyline induced wet-dog shakes which included head shake and whole body shake. p-Chloroamphetamine (PCA) (5 mg/kg) alone also produced wet-dog shakes in the vehicle-pretreated rats, but PCP (2.5-7.5 mg/kg) and tryptophan (100 mg/kg) alone did not. The number of wet-dog shakes significantly increased after the injection of PCA (2.5 and 5 mg/kg) in the reserpine-pretreated rats, in which the 5-hydroxyindoleacetic acid/serotonin (5-HT) ratio was significantly higher and postsynaptic 5-HT receptors were also in a state of supersensitivity, compared to that of the vehicle-pretreated rats. PCP (2.5-7.5 mg/kg) also produced wet-dog shakes in a dose-dependent fashion in rats after pretreatment with reserpine. Furthermore, PCP-induced wet-dog shakes were potentiated by imipramine, a 5-HT-uptake blocker, and prevented by mianserin, a 5-HT receptor-blocker. Tryptophan (100 mg/kg) alone produced wet-dog shakes in the reserpine-pretreated rats and it was enhanced in combination with imipramine. These results may indicate that the PCP-induced wet-dog shakes after reserpine withdrawal are due to an increased release of 5-HT from the functional pool and supersensitivity of postsynaptic 5-HT receptors.
本研究旨在评估在利血平治疗终止后，5-羟色胺能神经元在苯环己哌啶（PCP）诱导的大鼠湿狗样抖动中的作用。在用帕吉林预处理30分钟后给大鼠注射L-5-羟色氨酸（7.5-12.5mg/kg）可诱导湿狗样抖动，包括头部抖动和全身抖动。单独给予对氯苯丙胺（PCA）（5mg/kg）也可在给予赋形剂预处理的大鼠中产生湿狗样抖动，但单独给予PCP（2.5-7.5mg/kg）和色氨酸（100mg/kg）则不会。与给予赋形剂预处理的大鼠相比，在给予利血平预处理的大鼠中注射PCA（2.5和5mg/kg）后，湿狗样抖动的次数显著增加，其中5-羟吲哚乙酸/5-羟色胺（5-HT）比值显著更高，且突触后5-HT受体也处于超敏状态。在用利血平预处理的大鼠中，PCP（2.5-7.5mg/kg）也以剂量依赖性方式产生湿狗样抖动。此外，PCP诱导的湿狗样抖动可被5-HT摄取阻滞剂丙咪嗪增强，并被5-HT受体阻滞剂米安色林阻断。单独给予色氨酸（100mg/kg）可在给予利血平预处理的大鼠中产生湿狗样抖动，且与丙咪嗪联合使用时会增强。这些结果可能表明，利血平撤药后PCP诱导的湿狗样抖动是由于功能库中5-HT释放增加以及突触后5-HT受体超敏所致。
