[A biochemical theory of schizophrenia].
In addition to the dopamine hypothesis, a glutamate hypothesis has been recently discussed in the biochemical theories on the cause of schizophrenia. In schizophrenic patients less glutamic acid has been found in the cerebrospinal fluid. Glutamate is probably the most important excitatory transmitter of the mammalian forebrain. The liberation of glutamic acid in the striatum is inhibited by dopamine, more specifically by the D2 receptor, which is also though to be responsible for the antipsychotic effects of neuroleptic drugs. It seems possible that schizophrenia may be primarily caused by underfunction of glutamatergic corticostriatal and corticomesolimbic neurons rather than by overfunction of the dopaminergic system. The negative cognitive symptoms associated with schizophrenia would fit in with this hypothesis. The classical and the new atypical neuroleptic drugs show differential effects on glutamate and GABA in the brain tissue of the striatum and in the cerebrospinal fluid. Whereas sulpiride diminishes glutamate in the striatum and enhances glutamate in the cerebrospinal fluid, tiapride does not affect either of them. Correspondingly, tiapride does not show any antipsychotic effects. Haloperidol, on the other hand, enhances the GABA level in the striatum in a dose-related manner. These findings may perhaps prompt experimental research to find antipsychotic drugs with fewer side effects.
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006801:Humans; D019965:Neurocognitive Disorders / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D014150:Antipsychotic Agents; D005971:Glutamates; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D004298:Dopamine
Zur biochemischen Theorie der Schizophrenie.