Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice
Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice
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DOI：
10.1007/s00213-011-2207-6
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发表时间：
2011-06-01
影响因子：
3.4
通讯作者：
Aloyo, Vincent J.
中科院分区：
文献类型：
--
作者：
Dougherty, John P.;Aloyo, Vincent J.
5-羟色胺(5-羟色胺)2A受体与许多精神疾病有关，使其成为一个重要的临床相关靶点。本研究的目的是测定小鼠大脑皮质5-HT2A和5-HT2C受体的密度，建立小鼠5-HT2A受体的药理学图谱，并确定慢性药物治疗对5-HT2A受体密度和5-HT2A受体介导的行为的影响。通过取代[H-3]酮丝氨酸与几种配体的结合建立了药理图谱。慢性用5-HT2A/2C受体激动剂、2，5-二甲氧基-4-碘苯丙胺、5-HT2A受体拮抗剂、MDL 11939或赋形剂治疗后进行5-HT2A受体密度测定。小鼠的头部抽动反应(HTR)在选择的日子里被计数。小鼠有高的5-HT2a，但低的5-HT2C受体密度。小鼠5-HT2A受体的配基结合亲和力与大鼠的亲和力有关，但与兔或人的亲和力无关。与生理盐水处理的小鼠相比，慢性DOI处理的小鼠显示出更低的hTRs和5-HT2a受体密度。用MDL 11939慢性治疗后，受体密度没有变化。目前的研究提供了一些关于小鼠5-HT2A和5-HT2C受体的基本信息，并与大鼠、兔和人类进行了比较。目前的慢性激动剂治疗研究表明，5-HT2A受体在小鼠、大鼠和兔中有重要的相似之处，而拮抗剂治疗在兔身上显示出与先前研究的有趣的不同。
The serotonin (5-HT) 2A receptor is implicated in numerous psychiatric disorders, making it an important, clinically relevant target. Despite the availability of transgenic mouse lines, the native mouse 5-HT2A receptor is not well-characterized.The goals of the current study were to determine 5-HT2A and 5-HT2C receptor densities in mouse cortex, establish a pharmacological profile of the mouse 5-HT2A receptor, and determine the effects of chronic drug treatment on 5-HT2A receptor density and 5-HT2A receptor-mediated behavior.Receptor densities were determined in cortex and frontal cortex via saturation binding assays using [H-3]ketanserin or [H-3]mesulergine. A pharmacological profile was established by displacing [H-3]ketanserin binding with several ligands. Chronic treatment with 5-HT2A/2C receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-HT2A receptor antagonist, MDL 11939, or vehicle was followed by 5-HT2A receptor density determination. Head twitch responses (HTRs) were counted on select days.Mice had high 5-HT2A, but low 5-HT2C receptor densities. Ligand binding affinities for mouse 5-HT2A receptors correlated with rat, but not rabbit or human, affinities. Chronically DOI-treated mice displayed reduced HTRs and 5-HT2A receptor density compared to saline-treated mice. Receptor density was unchanged following chronic treatment with MDL 11939.The current study provides some basic information about mouse 5-HT2A and 5-HT2C receptors and provides comparisons to rats, rabbits, and humans. The current chronic agonist treatment study demonstrated an important similarity between the 5-HT2A receptor in mice, rats, and rabbits, while antagonist treatment revealed an interesting difference from previous studies in rabbits.