5-HT2C receptors in psychiatric disorders: A review

被引:81
作者
Chagraoui, A. [1 ,2 ]
Thibaut, F. [3 ,4 ]
Skiba, M. [1 ]
Thuillez, C. [5 ,6 ]
Bourin, M. [7 ]
机构
[1] Normandy Univ, Inst Res & Innovat Biomed, INSERM, U982,Lab Neuronal & Neuroendocrine Differentiat &, Caen, France
[2] Rouen Univ Hosp, Dept Med Biochem, Rouen, France
[3] Univ Paris 05, Univ Hosp Cochin, Dept Psychiat, Site Tarnier, Paris, France
[4] INSERM, U894, Lab Psychiat & Neurosci, Paris, France
[5] Rouen Univ Hosp, Dept Pharmacol, Rouen, France
[6] Normandy Univ, Inst Res & Innovat Biomed, INSERM, U1096,Lab New Pharmacol Targets Endothelial Prote, Caen, France
[7] Fac Med, EA Neurobiol Anxiety & Depress 3256, BP 53508,1 Rue Gaston Veil, F-44035 Nantes 01, France
关键词
5HT2C signaling; MRNA-editing; Gene polymorphism; Constitutive activity; Psychiatric disorders; OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN 2C RECEPTOR; FORCED SWIMMING TEST; NEUROLEPTIC MALIGNANT SYNDROME; ATYPICAL ANTIPSYCHOTIC-DRUGS; INCREASES DOPAMINE RELEASE; MAJOR DEPRESSIVE DISORDER; MESSENGER-RNA EXPRESSION; MEDIAL PREFRONTAL CORTEX; INVERSE AGONIST ACTIVITY;
D O I
10.1016/j.pnpbp.2015.12.006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
5-HT2Rs have a different genomic organization from other 5-HT2Rs. 5HT2CR undergoes post-transcriptional pre-mRNA editing generating diversity among RNA transcripts. Selective post-transcriptional editing could be involved in the pathophysiology of psychiatric disorders through impairment in G-protein interactions. Moreover, it may influence the therapeutic response to agents such as atypical antipsychotic drugs. Additionally, 5-HT2CR exhibits alternative splicing. Central serotonergic and dopaminergic systems interact to modulate normal and abnormal behaviors. Thus, 5HT2CR plays a crucial role in psychiatric disorders. 5HT2CR could be a relevant pharmacological target in the treatment of neuropsychiatric disorders. The development of drugs that specifically target 5-HT2C receptors will allow for better understanding of their involvement in the pathophysiology of psychiatric disorders including schizophrenia, anxiety, and depression. Among therapeutic means currently available, most drugs used to treat highly morbid psychiatric diseases interact at least partly with 5-HT2CRs. Pharmacologically, 5HT2CRs, have the ability to generate differentially distinct response signal transduction pathways depending on the type of 5HT2CR agonist. Although this receptor property has been clearly demonstrated, in vitro, the eventual beneficial impact of this property opens new perspectives in the development of agonists that could activate signal transduction pathways leading to better therapeutic efficiency with fewer adverse effects. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:120 / 135
页数:16
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