Nabeshima T, Ishikawa K, Yamaguchi K, Furukawa H, Kameyama T
Eur J Pharmacol. 1987 Jan 20;133(3):319-28. doi: 10.1016/0014-2999(87)90028-8.
This study was designed to assess whether phencyclidine (PCP)-induced behaviors in rats were potentiated after two days' withdrawal from chronic methysergide (a 5-HT2 receptor blocker) treatment (10 mg/kg per day i.p. for 12 days), in order to confirm the involvement of 5-hydroxytryptamine (5-HT) neurons in PCP actions. The PCP (10 mg/kg)-induced behaviors (head-twitch, head-weaving, turning and backpedalling) were attenuated by successive pretreatment with PCP (10 mg/kg per day i.p. for 12 days), while PCP- and 5-methoxy-N,N-dimethyltryptamine (2 mg/kg)-induced head-twitch increased significantly after the repeated methysergide treatment was stopped. The development of tolerance to PCP-induced head-twitch was antagonized by pretreatment with methysergide. Furthermore, Scatchard plots of specific [3H]ketanserin binding at the 5-HT2 receptors and [3H]PCP binding at the PCP receptors in the methysergide group revealed significant increases in binding capacity (Bmax) with no change in affinity (Kd). On the contrary, after development of tolerance to PCP, there were significant decreases in Bmax of [3H]ketanserin binding with no change in affinity. PCP can thus displace [3H]ketanserin at the 5-HT2 receptor site, but not [3H]5-HT at the 5-HT1 receptor site. These facts indicate that PCP may produce head-twitch via an agonistic interaction with 5-HT2 receptor sites.
本研究旨在评估大鼠在从慢性美西麦角（一种5 - HT2受体阻滞剂）治疗（每天腹腔注射10mg/kg，持续12天）撤药两天后，苯环己哌啶（PCP）诱导的行为是否会增强，以确认5 - 羟色胺（5 - HT）神经元在PCP作用中的参与情况。连续用PCP预处理（每天腹腔注射10mg/kg，持续12天）可减弱PCP（10mg/kg）诱导的行为（头部抽搐、头部摆动、转身和倒退），而在停止重复美西麦角治疗后，PCP和5 - 甲氧基 - N，N - 二甲基色胺（2mg/kg）诱导的头部抽搐显著增加。美西麦角预处理可拮抗对PCP诱导的头部抽搐耐受性的形成。此外，美西麦角组中5 - HT2受体处特异性[3H]酮色林结合以及PCP受体处[3H]PCP结合的Scatchard图显示结合能力（Bmax）显著增加，亲和力（Kd）无变化。相反，在对PCP产生耐受性后，[氚代]酮色林结合的Bmax显著降低，亲和力无变化。PCP因此可在5 - HT2受体位点取代[3H]酮色林，但不能在5 - HT1受体位点取代[3H]5 - HT。这些事实表明，PCP可能通过与5 - HT2受体位点的激动性相互作用产生头部抽搐。
