[Glutamatergic hypothesis of schizophrenia: psychoses induced by phencyclidine and cortical-subcortical imbalance].
Glutamatergic hypothesis stemmed from the observation of phencyclidine-induced psychosis. Phencyclidine is able to induce in healthy subjects negative and positive schizophrenic-like symptoms, as well as thought disorganization. Phencyclidine acts as an antagonist of NMDA receptor, one of the glutamatergic receptors. Experimental studies in animals have demonstrated that compartmental effect of phencyclidine is due to its action at striatal level, allowing the disinhibition of down-stream structures. The organization of the two striato-thalamocortical loops, which exert, respectively, a positive and negative retro-control on cortical activity, may explain how a glutamatergic deficiency induces both positive and negative symptoms. Positive symptoms could also be due to a secondary hyperdopaminergia, since a part of striatum, the striosomes, connected with limbic system, control the activity of dopaminergic neurons. This model validates the hypothesis that a single anomaly can lead to the different symptomatic dimensions of schizophrenia and supports the implication of basal ganglia in the expression of mental disease.
Service hospitalo-universitaire de Santé mentale, Hôpital Sainte-Anne, Paris.
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D000818:Animals; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects*; D005973:Glutamine / Q000502:physiology; D006801:Humans; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010622:Phencyclidine / Q000009:adverse effects*; D011605:Psychoses, Substance-Induced / Q000503:physiopathology* / Q000523:psychology; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced* / Q000503:physiopathology; D012565:Schizophrenic Psychology
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D010622:Phencyclidine; D004298:Dopamine
Hypothèse glutamatergique de la schizophrénie: des psychoses induites par la phencyclidine au déséquilibre cortico-sous-cortical.