期刊
PHARMACOLOGY & THERAPEUTICS
卷 150, 期 -, 页码 47-80出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2015.01.005
关键词
Abrupt discontinuation; Atypical antipsychotic; Functional neuroanatomy; Microdialysis; Nerve pathway; Pharmacircuitry
资金
- Science Foundation Ireland (SFI) [03/IN3/B403C]
- Higher Education Authority (HEA) Programme for Research in Third Level Institutions (PRTLI) (Cycle 3)
- National Development Programme (NDP)
- Enterprise Ireland (EI) [SC-2003-0029]
- Science Foundation Ireland (SFI) [03/IN3/B403C] Funding Source: Science Foundation Ireland (SFI)
Schizophrenia disease models are necessary to elucidate underlying changes and to establish new therapeutic strategies towards a stage where drug efficacy in schizophrenia (against all classes of symptoms) can be predicted. Here we summarise the evidence for a GABA dysfunction in schizophrenia and review the functional neuroanatomy of five pathways implicated in schizophrenia, namely the mesocortical, mesolimbic, ventral striopallidal, dorsal striopallidal and perforant pathways including the role of local GABA transmission and we describe the effect of clozapine on local neurotransmitter release. This review also evaluates psychotropic drug-induced, neurodevelopmental and environmental disease models including their compatibility with brain microdialysis. The validity of disease models including face, construct, etiological and predictive validity and how these models constitute theories about this illness is also addressed. A disease model based on the effect of the abrupt withdrawal of clozapine on GABA release is also described. The review concludes that while no single animal model is entirely successful in reproducing schizophreniform symptomatology, a disease model based on an ability to prevent and/or reverse the abrupt clozapine discontinuation-induced changes in GABA release in brain regions implicated in schizophrenia may be useful for hypothesis testing and for in vivo screening of novel ligands not limited to a single pharmacological class. (C) 2015 Elsevier Inc. All rights reserved.
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