Pharmacological studies of the acute and chronic effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity:: Role of 5-hydroxytryptamine_1A and 5-hydroxytryptamine_1B/1D receptors

作     者：McCreary, AC Bankson, MG Cunningham, KA 

作者机构：Univ Texas Med Branch Dept Pharmacol & Toxicol Galveston TX 77555 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第290卷第3期

页      面：965-973页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NIDA NIH HHS [DA 00260  DA 07287  DA 06511] Funding Source: Medline 

主　　题：3 4-亚甲二氧苯丙胺/药理学 行为 动物/药物作用 用药计划表 额叶/药物作用 额叶/代谢 吲哚类/药理学 运动活动/药物作用 恶二唑类/药理学 哌嗪类/药理学 吡啶类/药理学 大鼠 Sprague-Dawley 受体 血清素 5-HT1B 受体 血清素 5-HT1D 受体 血清素/分类 受体 血清素/生理学 受体 血清素 5-HT1 血清素类药/药理学 血清素拮抗药/药理学 血清素受体激动剂/药理学 氯化钠/药理学 动物 男(雄)性 大鼠 

摘      要：The 5-hydroxytryptamine(1B/1D) (5-HT1B/1D) antagonist 2 -methyl-4 -(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide (GR 127935) and 5-HT1A antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635) were used to assess whether hyperactivity induced by 3 mg/kg (+)-3,4-methylenedioxymethamphetamine [(+)-MDMA] is mediated by 5-HT1B/1D and/or 5-HT1A receptors. Activity in the periphery and center of an open field as well as rearing activity were measured in photobeam monitors. (+)-MDMA-induced peripheral and central activities were blocked by GR 127935 (0.3, 0.625, 1.25, and 2.5 mg/kg);central hyperactivity was blocked by 0.1, 0.3, and 0.625 mg/kg GR 127935. WAY 100635 (0.5-2 mg/kg) had little effect on (+)-MDMA-induced activity except for an enhancement of central activity at one dose (0.5 mg/kg). Central activity induced by (+)-MDMA increased from day 1 to day 5 of treatment with (+)-MDMA (3 mg/kg), whereas peripheral, central, and rearing activity significantly increased in (+)-MDMA-treated rats pretreated daily with GR 127935 (2.5 mg/kg). Withdrawal from (+)-MDMA, but not GR 127935 + (+)-MDMA, pretreatment was associated with heightened hyperactivity induced by the 5-HT1B/1A agonist RU 24969 (2 mg/kg i.p.);treatments were not associated with alterations in 5-HT and 5-hydroxyindoleacetic acid content or turnover in frontal cortex. These data support a role for 5-HT1B/1D in mediating the acute hyperactivity evoked by (+)-MDMA. The development of sensitization to (+)-MDMA was associated with supersensitivity to a 5-HT1B/1A agonist, suggesting that these receptors may contribute to sensitization. However, sensitization to (+)-MDMA developed even under conditions of 5-HT1B/1D receptor blockade, which is somewhat counter to this speculation. Perhaps, under circumstances of continued 5-HT1B/1D. blockade, other mechanisms (e.g., dopamine) predominate in the progr