Pharmacogenetic evidence for the involvement of 5-hydroxytryptamine (serotonin)-1B receptors in the mediation of morphine antinociceptive sensitivity

作     者：Hain, HS Belknap, JK Mogil, JS 

作者机构：Oregon Hlth & Sci Univ Vet Affairs Med Ctr Dept Behav Neurosci Portland OR 97201 USA Univ Illinois Dept Psychol Champaign IL 61820 USA Univ Illinois Neurosci Program Champaign IL 61820 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291卷第2期

页      面：444-449页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：NIAAA NIH HHS [P60 AA010760] Funding Source: Medline NIDA NIH HHS [T32DA07262, DA11394] Funding Source: Medline 

主　　题：8-羟-2-(二-n-丙胺)四氢萘/药理学 镇痛药/药理学 剂量效应关系 药物 药物相互作用 小鼠 近交C57BL 小鼠 近交DBA 吗啡/药理学 恶二唑类/药理学 哌嗪类/药理学 受体 血清素/遗传学 受体 血清素/生理学 敏感性与特异性 血清素拮抗药/药理学 种特异性 时间因素 动物 小鼠 

摘      要：Morphine antinociception has been shown to be influenced significantly by genetic factors, now beginning to be identified in mice. A recent quantitative trait locus analysis revealed a significant statistical association between morphine antinociceptive magnitude and a region of mouse chromosome 9. This region contains the Htr1b gene, which encodes the 5-hydroxytryptamine (serotonin)-1B (5- HT1B) receptor subtype. To investigate the possibility that Htr1b represents the quantitative trait locus, C57BL/6 and DBA/2 inbred strains, the progenitors of the original quantitative trait locus mapping populations, were administered a novel 5- HT1B receptor antagonist (GR127935) concomitant with morphine. These mice are known to differ in morphine antinociceptive sensitivity on thermal pain assays (DBA/2 high;C57BL/6 low). GR127935 caused a dose-dependent antagonism (both reversal and prevention) of morphine antinociception in DBA/2 mice but had no effect in C57BL/6 mice. However, a 5-hydroxytryptamine-1A subtype (5- HT1A) receptor agonist, 8-hydroxydipropylaminotetralin, reversed morphine antinociception equally in the two strains. DBA/2 mice also exhibited significantly greater antinociception than did C57BL/6 mice from the administration of a 5- HT1B agonist, CGS12066. These data collectively support a role for 5- HT1B receptors in the mediation of morphine antinociception and support the contention that polymorphisms in the Htr1b gene may underlie individual differences in morphine sensitivity.