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Titolo:
Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia
Autore:
Greene, R;
Indirizzi:
Harvard Univ, Dept Psychiat, Sch Med, Brockton, MA USA Harvard Univ Brockton MA USA v, Dept Psychiat, Sch Med, Brockton, MA USA VAMC, Brockton, MA USA VAMC Brockton MA USAVAMC, Brockton, MA USA
Titolo Testata:
HIPPOCAMPUS
fascicolo: 5, volume: 11, anno: 2001,
pagine: 569 - 577
SICI:
1050-9631(2001)11:5<569:CAONHI>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACIDIC DIPEPTIDASE ACTIVITY; N-ACETYLASPARTYLGLUTAMATE IMMUNOREACTIVITY; RAT ENTORHINAL CORTEX; D-ASPARTATE RECEPTORS; SPINAL-CORD; GLYCINE TRANSPORTER; NEGATIVE SYMPTOMS; MOUSE-BRAIN; L-GLUTAMATE; NEURONS;
Keywords:
EPSC; NMDA antagonist; ketamine; glycine; place cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Greene, R Harvard Univ, Dept Psychiat, Sch Med, 940 Belmont St, Brockton, MA USA Harvard Univ 940 Belmont St Brockton MA USA t, Brockton, MA USA
Citazione:
R. Greene, "Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia", HIPPOCAMPUS, 11(5), 2001, pp. 569-577

Abstract

NMDA antagonists provide the best pharmacological model of psychosis-related schizophrenia. Data from circuit analysis of the effects of the antagonism of NMDA receptors in the CAI region of the hippocampus of rats in vitro suggest a hypothesis concerning cortical circuit dysfunction responsible for NMDA antagonist-dependent psychosis, relevant to the psychosis associatedwith schizophrenia. The NMDA antagonists may act by causing a selective, partial, disinhibition of cortical projection cells. The effects are partially due to the partial role of NMDA-dependent transmission in the excitatoryglutamate drive of interneurons. Characterization of the selectivity is incomplete, but includes disinhibition of the recurrent inhibitory circuit and is concentration-sensitive. It may result from differences in NMDA receptors (NMDARs) on interneurons. At higher concentrations, antagonism of all NMDA-dependent transmission results in anesthesia. At low concentration, selective blockade of NMDA-dependent LTP of the recurrent inhibitory circuit may disrupt particular aspects of information processing involving learning and/or memory, consistent with the generation of abnormal associations. An endogenous peptide, NAAG, is shown to antagonize NMDARs in a manner similarto known psychotogenic agents like ketamine or phencyclidine. Finally, mechanisms that could enhance NMDAR function are discussed as possible therapeutic strategies for psychosis. Published 2001 Wiley-Liss, lnc.

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Documento generato il 26/01/20 alle ore 00:50:27