The role of serotonin-2 (5-HT2) and dopamine receptors in the behavioral actions of the 5-HT2A/2C agonist, DOI, and putative 5-HT2C inverse agonist, SR46349B.
The role of serotonin-2 (5-HT2) and dopamine receptors in the behavioral actions of the 5-HT2A/2C agonist, DOI, and putative 5-HT2C inverse agonist, SR46349B.
复制标题
血清素 2 (5-HT2) 和多巴胺受体在 5-HT2A/2C 激动剂 DOI 和推定的 5-HT2C 反向激动剂 SR46349B 的行为作用中的作用。
DOI：
10.1007/s00213-010-1928-2
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发表时间：
2011
影响因子：
3.4
通讯作者：
Aloyo,VincentJ
中科院分区：
文献类型：
--
作者：
Scarlota,LauraC;Harvey,JohnA;Aloyo,VincentJ
RationaleAtypical antipsychotic efficacy is often attributed to actions at serotonin-2 (5-HT2) and dopamine receptors, indicating a potential benefit of understanding the interplay between these systems. Currently, it is known that 5-HT2receptors modulate dopamine release, although the role of specific dopamine receptors in 5-HT2-mediated behavior is not well understood.ObjectivesWe examined the role of 5-HT2A, 5-HT2C, and dopamine (D1 and D2) receptors in the behavioral response to a 5-HT2A/2Cagonist (DOI) and 5-HT2A/2Cantagonist (SR46349B).Materials and methodsEffects were assessed by measuring rabbit head bobs (previously characterized as 5-HT2Areceptor-mediated) and body shakes (5-HT2C-mediated).ResultsAs expected, DOI produced head bobs and body shakes, and these DOI-elicited behaviors were attenuated by the SR46349B pretreatment. Unexpectedly, SR46349B also induced head bobs when administered alone. However, SR46349B-elicited head bobs are distinguishable from those produced by DOI since the 5-HT2Aantagonist, ketanserin, only attenuated DOI-elicited head bobs. Conversely, 5-HT2Cligands (SB242084 and SB206553) inhibited SR46349B but not DOI-induced head bobs. Furthermore, when administered alone, SB206553 (a 5-HT2Cinverse agonist) produced head bobs, indicating the behavior can be either 5-HT2Aor 5-HT2Cmediated. Next, it was revealed that D1 and D2 receptors play a role in DOI-elicited head bobs, but only D1 receptors are required for SR46349B-elicited head bobs.Conclusions5-HT2Areceptor agonism and 5-HT2Cinverse agonism produce the same behavior, likely due to similar downstream actions at D1 receptors. Consequently, 5-HT2Cagonism or D1 agonism may be effective therapies for disorders, such as schizophrenia, currently being treated with 5-HT2Aantagonists.
