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苯环利定通过与利血平化大鼠的5-HT1和5-HT2受体相互作用诱导头部摆动和头部抽搐。

Phencyclidine-induced head-weaving and head-twitch through interaction with 5-HT1 and 5-HT2 receptors in reserpinized rats.

作者信息

Yamaguchi K, Nabeshima T, Ishikawa K, Yoshida S, Kameyama T

机构信息

Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.

出版信息

Neuropharmacology. 1987 Oct;26(10):1489-97. doi: 10.1016/0028-3908(87)90168-7.

Abstract

Phencyclidine mainly produced head-weaving and head-twitches at doses of 5-7.5 mg/kg and of 7.5-12.5 mg/kg, respectively. Phencyclidine-induced head-twitches and head-weaving were blocked by pretreatment with ritanserin (1 mg/kg), a selective serotonin (5-HT)2 receptor antagonist and with pindolol (20 mg/kg, s.c.), a 5-HT1 receptor antagonist, respectively. In reserpine-pretreated rats, the degree of utilization of 5-HT and the number of 5-HT1 ([3H]5-HT) and 5-HT2 ([3H]ketanserin) binding sites were significantly increased compared with the figures for the vehicle-pretreated rats. The intensity of phencyclidine-induced head-weaving (at the dose of 2.5 mg/kg) and head-twitch (at the doses of 2.5 and 5 mg/kg) was significantly increased in reserpine-pretreated rats compared with that of vehicle-pretreated rats. Furthermore, in the reserpine-pretreated rats, the intensity of phencyclidine (1.25 mg/kg)-induced head-weaving and head-twitches was increased in combination with imipramine, while the intensity of phencyclidine (2.5 mg/kg)-induced head-weaving and head-twitch was decreased by pretreatment with mianserin, a non-selective 5-HT receptor antagonist. These results indicate that phencyclidine induced head-weaving by interacting with 5-HT1 receptors, indirectly after the release of 5-HT and/or with some other mechanisms and induced head-twitch by interacting with 5-HT2 receptors directly and/or indirectly.

摘要

苯环利定分别在5 - 7.5毫克/千克和7.5 - 12.5毫克/千克的剂量下主要引起头部摆动和头部抽搐。苯环利定诱导的头部抽搐和头部摆动分别被选择性5-羟色胺(5-HT)2受体拮抗剂利坦色林(1毫克/千克)预处理和5-HT1受体拮抗剂吲哚洛尔(20毫克/千克,皮下注射)阻断。在利血平预处理的大鼠中,与载体预处理的大鼠相比,5-羟色胺的利用程度以及5-HT1([3H]5-羟色胺)和5-HT2([3H]酮色林)结合位点的数量显著增加。与载体预处理的大鼠相比,利血平预处理的大鼠中苯环利定(2.5毫克/千克剂量)诱导的头部摆动和(2.5和5毫克/千克剂量)头部抽搐的强度显著增加。此外,在利血平预处理的大鼠中,苯环利定(1.25毫克/千克)诱导的头部摆动和头部抽搐的强度在与丙咪嗪联合使用时增加,而苯环利定(2.5毫克/千克)诱导的头部摆动和头部抽搐的强度在被非选择性5-HT受体拮抗剂米安色林预处理后降低。这些结果表明,苯环利定通过与5-HT1受体相互作用,在5-羟色胺释放后间接和/或通过其他一些机制诱导头部摆动,并通过直接和/或间接与5-HT2受体相互作用诱导头部抽搐。

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