[Deficit schizophrenia: from pharmacology to clinical practice].
After having rapidly recapitulated the various arguments which suggest that meso-subcortical dopaminergic neurons are hyperreactive in the productive form of schizophrenia, we suggest in this article that dysfunction of noradrenergic neurons gives rise to this disorder whether of the productive or deficitary variety. In the specific case of deficitary schizophrenia, noradrenergic transmission appears to be desensitized, most likely following intense and repeated activation. Our results in fact show that activation of noradrenergic neurons inhibits cortical dopaminergic transmission mediated by D1 receptors and enhances the functional role of subcortical dopaminergic neurons. On the basis of these data, the lack of noradrenergic transmission would lead to a cortico/subcortical imbalance in favour of cortical areas. Deficitary schizophrenics would then find themselves stalled in a short-term memory situation without external data they could process. The therapeutic effect of substituted benzamides on negative schizophrenic patients may be explained by the observation that these products increase the release of noradrenaline in the frontal cortex and reactive subcortical dopaminergic neurons by blocking D2-type autoreceptors.
Tassin
J P
JP
INSERM U114, Collège de France, Paris.
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D009638:Norepinephrine / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D014150:Antipsychotic Agents; D001549:Benzamides; D017447:Receptors, Dopamine D1; D004298:Dopamine; D009638:Norepinephrine
Schizophrénies déficitaires: de la pharmacologie à la clinique.