Nabeshima T, Yamaguchi K, Ishikawa K, Furukawa H, Kameyama T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
J Pharmacol Exp Ther. 1987 Dec;243(3):1139-46.
Phencyclidine (PCP)-induced behaviors were compared with 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)- and p-chloroamphetamine-induced behaviors in rats pretreated with ritanserin or 5,7-dihydroxytryptamine (5,7-DHT) in order to investigate whether PCP interacts with 5-hydroxytryptamine2 (5-HT2) receptors. Head-twitch and wet-dog shake induced by p-chloroamphetamine, a 5-HT releaser, and head-twitch induced by PCP were blocked completely by pretreatment with ritanserin, a specific 5-HT2 receptor blocker, but other behaviors induced by p-chloroamphetamine, PCP and 5-MeODMT, a 5-HT agonist, were not. The intensity of head-weaving, turning, backpedalling and hind-limb abduction induced by 5-MeODMT and the intensity of head-weaving, turning and head-twitch induced by PCP were markedly greater in the rats 2 weeks after the 5,7-DHT, a 5-HT neurotoxin-injection. Contrarily, 5-HT-mediated behaviors induced by p-chloroamphetamine were attenuated in the 5,7-DHT-treated rats. 5,7-DHT-treatment increased the number of 5-HT1 ([3H]-5-HT), 5-HT2 ([3H]ketanserin) and PCP ([3H]PCP) binding sites in the synaptic membrane of rat brain, but decreased the brain level of 5-HT (41% of control). These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats.
为研究苯环己哌啶（PCP）是否与5-羟色胺2（5-HT2）受体相互作用，比较了PCP诱导的行为与5-甲氧基-N,N-二甲基色胺（5-MeODMT）和对氯苯丙胺诱导的行为，实验对象为预先用利坦色林或5,7-二羟色胺（5,7-DHT）处理过的大鼠。对氯苯丙胺（一种5-HT释放剂）诱导的头部抽搐和湿狗样抖动以及PCP诱导的头部抽搐，可被特异性5-HT2受体阻断剂利坦色林预处理完全阻断，但对氯苯丙胺、PCP和5-MeODMT（一种5-HT激动剂）诱导的其他行为则未被阻断。5,7-DHT（一种5-HT神经毒素）注射2周后的大鼠，5-MeODMT诱导的头部摆动、转身、倒退和后肢外展的强度以及PCP诱导的头部摆动、转身和头部抽搐的强度明显更大。相反，在5,7-DHT处理的大鼠中，对氯苯丙胺诱导的5-HT介导的行为减弱。5,7-DHT处理增加了大鼠脑突触膜中5-HT1（[3H]-5-HT）、5-HT2（[3H]酮色林）和PCP（[3H]PCP）结合位点的数量，但降低了脑内5-HT水平（为对照组的41%）。这些结果可能表明，PCP作为一种5-HT2激动剂通过5-HT2受体诱导头部抽搐，并且PCP在大鼠中通过5-HT1受体和/或其他一些机制诱导头部摆动和转身。
