Serotonin 2C receptor agonists and the behavioural satiety sequence in mice
Serotonin 2C receptor agonists and the behavioural satiety sequence in mice
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DOI：
10.1016/s0091-3057(01)00709-2
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发表时间：
2002-04-01
影响因子：
3.6
通讯作者：
Clifton, PG
中科院分区：
文献类型：
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作者：
Hewitt, KN;Lee, MD;Clifton, PG
本文报告的研究检查了5-羟色胺（5-HT）（2C）受体亚型在控制小鼠摄食行为中的作用。进行行为饱腹感序列（BSS）和摄食量测量，比较选择性5-HT，c受体激动剂（S）-2（6-氯-5-氟-吲哚-1-基）-1-甲基乙胺盐酸盐（Ro 60-0175; 1.0、3.0和10.0 mg/kg）和D-芬氟拉明（3.0 mg/kg）。Ro 60-0175导致摄食量呈剂量依赖性减少。Ro 60-0175（3.0 mg/kg）对BSS的影响与D-芬氟拉明（3.0 mg/kg）的低吞噬作用相似。在第二项实验中，通过选择性5-HT预处理减弱Ro 60-0175（5.6 mg/ kg）对摄食的特定影响，c.受体拮抗剂6-氯-5-甲基-1-[2-（2-甲基吡啶-3-氧基）-吡啶-5-基氨基甲酰基]二氢吲哚（SB 242084; 0.5 mg/kg）。5-HT、B c受体激动剂1-（间氯苯基）哌嗪（mCPP; 3 mg/kg）也导致摄食量显著减少，SB 242084（0.5 mg/kg）可减弱该作用。选择性5-HT 1B 1D拮抗剂2 '甲基-4'（5-甲基-[1，2，4]恶二唑-3-基）-联苯-4-甲酸[4-（2-（三氟甲基）苯基）氨基]-N-（2-（三氟甲基）苯基）-N-（三氟甲基）氨基）-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-（三氟甲基（5-甲氧基-3-（4-甲基-哌嗪-1-基）-苯基]酰胺（GR 127935; 3.0 mg/kg），成功地减弱了5-HT（1B）激动剂5-甲氧基-3（1，2，3，6-四氢吡啶-4-基）-1H-吲哚（RU 24969; 5.0 mg/kg）未能减轻mCPP诱导的食欲减退。这些数据表明，Ro 60-0175和mCPP诱导的小鼠摄食量减少是通过激活5-HT，c受体介导的，5-HT 1B受体的刺激在mCPP诱导的摄食量减少中仅起次要作用。(C)2002年爱思唯尔科技有限公司All rights reserved.
The studies reported here examined the role of the 5-hydroxytryptamine (5-HT)(2C) receptor subtype in the control of ingestive behaviour in mice. Behavioural satiety sequence (BSS) and food intake measurements were taken, comparing the selective 5-HT,c receptor agonist (S)-2(6-chloro-5-fluoro-indol-1-yl)-1-methylethylamine hydrochloride (Ro 60-0175; 1.0, 3.0 and 10.0 mg/kg) and D-fenfluramine (3.0 mg/kg). Ro 60-0175 produced a dose-dependent decrease in food intake. The effects of Ro 60-0175 (3.0 mg/kg) on the BSS were similar to the hypophagic effects of D-fenfluramine (3.0 mg/kg). In a second experiment, the specific effects on feeding produced by Ro 60-0175 (5.6 mg/ kg) were attenuated by pretreatment with the selective 5-HT,c. receptor antagonist 6-chloro-5-methyl- 1-[2(2-methylpyridyl-3-oxy)-pytid-5-yl carbamoyl] indoline (SB 242084; 0.5 mg/kg). The 5-HT, B c receptor agonist 1-(m-chlorophenyl)piperazine (mCPP; 3 mg/kg) also produced a substantial decrease in food intake, which was attenuated by SB 242084 (0.5 mg/kg). A dose of the selective 5-HT1B 1D antagonist 2'methyl-4'(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-(5-methoxy-3-(4-methyl-piperazin-l-yl)-phenyl]amide (GR 127935; 3.0 mg/kg) that successfully attenuated the action of the 5-HT (1B) agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969; 5.0 mg/kg) failed to attenuate mCPP-induced hypophagia. These data suggest that Ro 60-0175- and mCPP-induced hypophagia in mice are mediated via activation of 5-HT,c receptors and that stimulation of 5-HT1B receptors plays only a minor role in mCPP-induced hypophagia. (C) 2002 Elsevier Science Inc. All rights reserved.