Nabeshima T, Fukaya H, Yamaguchi K, Ishikawa K, Furukawa H, Kameyama T
Eur J Pharmacol. 1987 Mar 3;135(1):23-33. doi: 10.1016/0014-2999(87)90753-9.
In rats treated with phencyclidine (PCP) repeatedly (PCP 10 mg/kg per day for 14 days), the back-pedalling, head-weaving and turning induced by PCP were attenuated (tolerance), while PCP-induced sniffing, rearing and ambulation were potentiated (supersensitivity). The behavior induced by the direct and indirect serotonin (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine and p-chloroamphetamine, was attenuated, while the sniffing, rearing or licking induced by the direct and indirect dopamine (DA) agonists, apomorphine and methamphetamine, were potentiated in the chronic PCP-treated rats. The DA and 5-HT contents in the nucleus accumbens and the ratio of HVA to DA in the striatum increased following the repeated PCP administration. Pentobarbital-induced sleep time did not change in the chronic PCP-treated rats as compared with the control rats. In addition, there was no significant difference between the disappearance rate of PCP in the brain of the rats treated with PCP repeatedly and the rate in the control rats. These results suggest that functional changes in the dopaminergic and serotonergic neuronal systems develop on repeated administration of PCP but that such changes do not develop in the hepatic drug-metabolizing system. In addition, tolerance develops in the serotonergic neuronal system while supersensitivity develops in the dopaminergic neuronal system. Biochemical findings suggest that increased mesolimbic dopaminergic neuronal function plays an important role in the development of the supersensitivity.
在用苯环己哌啶（PCP）反复处理的大鼠（每天10mg/kg PCP，共14天）中，PCP诱导的倒退、头部摆动和转身行为减弱（耐受性），而PCP诱导的嗅探、竖毛和走动行为增强（超敏反应）。直接和间接5-羟色胺（5-HT）激动剂5-甲氧基-N，N-二甲基色胺和对氯苯丙胺诱导的行为减弱，而直接和间接多巴胺（DA）激动剂阿扑吗啡和甲基苯丙胺诱导的嗅探、竖毛或舔舐行为在慢性PCP处理的大鼠中增强。反复给予PCP后，伏隔核中的DA和5-HT含量以及纹状体中高香草酸与DA的比值增加。与对照大鼠相比，慢性PCP处理的大鼠中戊巴比妥诱导的睡眠时间没有变化。此外，反复给予PCP的大鼠大脑中PCP的消失率与对照大鼠的消失率之间没有显著差异。这些结果表明，反复给予PCP会导致多巴胺能和5-羟色胺能神经元系统发生功能变化，但肝脏药物代谢系统中不会发生这种变化。此外，5-羟色胺能神经元系统出现耐受性，而多巴胺能神经元系统出现超敏反应。生化研究结果表明，中脑边缘多巴胺能神经元功能增强在超敏反应的发生中起重要作用。
