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动物模型中的血清素能药理学:从行为障碍到运动障碍

Serotonergic pharmacology in animal models: from behavioral disorders to dyskinesia.

作者信息

Beaudoin-Gobert Maude, Sgambato-Faure Véronique

机构信息

Centre de Neuroscience Cognitive, Centre National de la Recherche Scientifique UMR 5229, Bron cedex F-69675, France; Université Lyon 1, France.

Centre de Neuroscience Cognitive, Centre National de la Recherche Scientifique UMR 5229, Bron cedex F-69675, France; Université Lyon 1, France.

出版信息

Neuropharmacology. 2014 Jun;81:15-30. doi: 10.1016/j.neuropharm.2014.01.031. Epub 2014 Jan 30.

Abstract

Serotonin (5-HT) dysfunction has been involved in both movement and behavioral disorders. Serotonin pharmacology improves dyskinetic movements as well as depressive, anxious, aggressive and anorexic symptoms. Animal models have been useful to investigate more precisely to what extent 5-HT is involved and whether drugs targeting the 5-HT system can counteract the symptoms exhibited. We review existing rodent and non-human primate (NHP) animal models in which selective 5-HT or dual 5-HT-norepinephrine (NE) transporter inhibitors, as well as specific 5-HT receptors agonists and antagonists, monoamine oxidase A inhibitors (IMAO-A) and MDMA (Ecstasy) have been used. We review overlaps between the various drug classes involved. We confront behavioral paradigms and treatment regimen. Some but not all animal models and associated pharmacological treatments have been extensively studied in the litterature. In particular, the impact of selective serotonin reuptake inhibitors (SSRI) has been extensively investigated using a variety of pharmacological or genetic rodent models of depression, anxiety, aggressiveness. But the validity of these rodent models is questioned. On the contrary, few studies did address the potential impact of targeting the 5-HT system on NHP models of behavioral disorders, despite the fact that those models may match more closely to human pathologies. Further investigations with carefull behavioral analysis will improve our understanding of neural bases underlying the pathophysiology of movement and behavioral disorders.

摘要

血清素(5-羟色胺,5-HT)功能障碍与运动和行为障碍均有关联。血清素药理学可改善运动障碍以及抑郁、焦虑、攻击和厌食症状。动物模型有助于更精确地研究5-HT在多大程度上参与其中,以及针对5-HT系统的药物是否能够抵消所表现出的症状。我们综述了现有的啮齿动物和非人类灵长类动物(NHP)模型,其中使用了选择性5-HT或5-HT-去甲肾上腺素(NE)双重转运体抑制剂,以及特定的5-HT受体激动剂和拮抗剂、单胺氧化酶A抑制剂(IMAO-A)和摇头丸(MDMA)。我们综述了所涉及的各类药物之间的重叠情况。我们对比了行为范式和治疗方案。部分但并非所有动物模型及相关药物治疗已在文献中得到广泛研究。特别是,选择性5-羟色胺再摄取抑制剂(SSRI)的影响已在多种抑郁症、焦虑症、攻击性的药理学或基因啮齿动物模型中得到广泛研究。但这些啮齿动物模型的有效性受到质疑。相反,尽管非人类灵长类动物模型可能与人类病理学更为匹配,但针对5-HT系统对行为障碍的非人类灵长类动物模型潜在影响的研究却很少。通过仔细的行为分析进行进一步研究,将增进我们对运动和行为障碍病理生理学潜在神经基础的理解。

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