Nabeshima T, Yamaguchi K, Hiramatsu M, Amano M, Furukawa H, Kameyama T
Pharmacol Biochem Behav. 1984 Sep;21(3):401-8. doi: 10.1016/s0091-3057(84)80102-1.
Administration of 5-10 mg/kg of phencyclidine (PCP) caused stereotyped behaviors including sniffing, backpedalling, head weaving and turning in rats. The PCP-induced stereotyped behaviors (backpedalling, head weaving and turning) were attenuated by serotonin (5-HT) depleters [reserpine, p-chlorophenylalanine, p-chloroamphetamine (PCA)] and 5-HT receptor antagonist (cyproheptadine). PCP-induced head weaving and turning were potentiated by 5-HT precursor (tryptophan) and 5-HT releaser (PCA). PCP-induced head weaving were potentiated also by monoamine oxidase inhibitor (pargyline) and 5-HT reuptake inhibitor (imipramine). PCP 5-10 mg/kg significantly increased the content of 5-HT in the thalamus/hypothalamus at 30 and 60 min after the injection, except PCP 5 mg/kg at 60 min. PCP 7.5 and 10 mg/kg increased the rate of increment of 5-HT by pargyline in the thalamus/hypothalamus at 30 and 60 min after the injection, respectively. PCP 10 mg/kg significantly increased the contents of 5-HIAA in the striatum and thalamus/hypothalamus at 30 min, but decreased that of 5-HIAA in all discrete brain areas except the stratium at 60 min after the injection. PCP also significantly prevented the depletion of 5-HT by PCA in all discrete brain areas except the stratium at 60 min after the injection. From these results, PCP-induced stereotyped behaviors are related to an increased serotonergic neuronal activity due to 5-HT releasing action and/or inhibitory action of 5-HT uptake-by this drug.
给大鼠注射5-10毫克/千克的苯环己哌啶(PCP)会引发刻板行为,包括嗅探、倒退、头部摆动和转身。PCP诱导的刻板行为(倒退、头部摆动和转身)会被血清素(5-HT)耗竭剂[利血平、对氯苯丙氨酸、对氯苯丙胺(PCA)]和5-HT受体拮抗剂(赛庚啶)减弱。PCP诱导的头部摆动和转身会被5-HT前体(色氨酸)和5-HT释放剂(PCA)增强。PCP诱导的头部摆动也会被单胺氧化酶抑制剂(帕吉林)和5-HT再摄取抑制剂(丙咪嗪)增强。注射后30分钟和60分钟时,5-10毫克/千克的PCP显著增加了丘脑/下丘脑内5-HT的含量,但注射后60分钟时,5毫克/千克的PCP除外。注射后30分钟和60分钟时,7.5毫克/千克和l0毫克/千克的PCP分别增加了帕吉林在丘脑/下丘脑内使5-HT增加的速率。注射后30分钟时,10毫克/千克的PCP显著增加了纹状体和丘脑/下丘脑内5-羟吲哚乙酸(5-HIAA)的含量,但注射后60分钟时,除纹状体外,PCP降低了所有离散脑区中5-HIAA的含量。注射后60分钟时,除纹状体外,PCP还显著阻止了PCA在所有离散脑区中对5-HT的耗竭。从这些结果来看,PCP诱导的刻板行为与该药物的5-HT释放作用和/或5-HT摄取抑制作用导致的血清素能神经元活动增加有关。