Serotonin1A Receptors in the Pathophysiology of Schizophrenia: Development of Novel Cognition-Enhancing Therapeutics

被引：39

作者：

Sumiyoshi, Tomiki ^{[1
]}

Bubenikova-Valesova, Vera ^{[2
,3
]}

Horacek, Jiri ^{[2
,3
]}

Bert, Bettina ^{[4
]}

机构：

[1] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Neuropsychiat, Toyama, Japan

[2] Prague Psychiat Ctr, Prague, Czech Republic

[3] Ctr Neuropsychiat Studies, Prague, Czech Republic

[4] Free Univ Berlin, Sch Vet Med, Inst Pharmacol & Toxicol, D-1000 Berlin, Germany

来源：

ADVANCES IN THERAPY | 2008年 / 25卷 / 10期

基金：

日本学术振兴会;

关键词：

5-HT1A; 5-HT receptors; cognition; schizophrenia; serotonin; translational research;

D O I：

10.1007/s12325-008-0102-2

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Serotonin (5-HT) receptors have been suggested to play key roles in psychosis, cognition, and mood via influence on neurotransmitters, synaptic integrity, and neural plasticity. Specifically, genetic evidence indicates that 5-HT1A, 5-HT2A, and 5-HT2C receptor single-nucleotide polymorphisms (SNPs) are related to psychotic symptoms, cognitive disturbances, and treatment response in schizophrenia. Data from animal research suggest the role of 5-HT in cognition via its influence on dopaminergic, cholinergic, glutamatergic, and GABAergic function. This article provides up-to-date findings on the role of 5-HT receptors in endophenotypic variations in schizophrenia and the development of newer cognition-enhancing medications, based on basic science and clinical evidence. Imaging genetics studies on associations of polymorphisms of several 5-HT receptor subtypes with brain structure, function, and metabolism suggest a role for the prefrontal cortex and the parahippocampal gyrus in cognitive impairments of schizophrenia. Data from animal experiments to determine the effect of agonists/antagonists at 5-HT1A, 5-HT2A, and 5-HT2C receptors on behavioral performance in animal models of schizophrenia based on the glutamatergic hypothesis provide useful information. For this purpose, standard as well as novel cognitive tasks provide a measure of memory/information processing and social interaction. In order to scrutinize mixed evidence for the ability of 5-HT1A agonists/antagonists to improve cognition, behavioral data in various paradigms from transgenic mice overexpressing 5-HT1A receptors provide valuable insights. Clinical trials reporting the advantage of 5-HT1A partial agonists add to efforts to shape pharmacologic perspectives concerning cognitive enhancement in schizophrenia by developing novel compounds acting on 5-HT receptors. Overall, these lines of evidence from translational research will facilitate the development of newer pharmacologic strategies for the treatment of cognitive disturbances of schizophrenia.

引用

页码：1037 / 1056

页数：20

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