Strong evidence exists for disturbed functional connectivity of cortical microcircuits - particularly of prefrontal cortex. Dopamine, long implicated in antipsychotic drug effects, is crucially involved in optimizing signal-to-noise ratio of local cortical micro-circuits. This action of dopamine is achieved by means of D1- and D2-receptor-mediated effects on pyramidal and local circuit neurons, which mediate recurrent inhibition and thus contribute to the stability of cortical representations of external and internal stimuli. In schizophrenia, a diminished cortical dopamine D1/D2 activation ratio - in concert with altered GABAergic and glutamatergic transmission - appear to critically interfere with this process.
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Georg Winterer, MD, PhD
Dept. of Psychiatry
Heinrich-Heine University Hospital
Bergische Landstr. 2
D-40629 Duesseldorf
Germany
Phone: +49-(0)211-922-3463
Fax: +49-(0)211-922-3498
Email: georg.winterer@uni-duesseldorf.de
