NMDA-hyposensitivity in whole blood platelets of amisulpride-treated schizophrenics

Aims of this study were to (1) set up a flow cytometric method to determine the NMDA-dependent intracellular Calcium ([Ca++]i) mobilization in platelets, and (2) investigate platelet glutamate sensitivity in healthy controls and schizophrenics. Anticoagulated whole blood was incubated with Fluo-4 and stained with a platelet-specific antibody. In probes of healthy subjects (n=5) the NMDA antagonist MK-801 or the dopamine antagonist amisulpride were added prior to glutamate-stimulation. After determination of baseline platelet Fluo-4 fluorescence, glutamate was added and the percentual changes from baseline determined. [Ca++]i response to glutamate was compared between amisulpride-treated schizophrenic patients (n=16) and matched controls (n=16). Stimulation with glutamate led dose-dependently to [Ca++]i mobilization in both healthy controls and patients. This was inhibited by in vitro addition of MK-801, but unaffected by the in vitro addition of amisulpride. The glutamate dependent [Ca++]i response was significantly reduced in patients' platelets. The presented method allows to measure a [Ca++]i response in whole blood platelets, specific to glutamate stimulation. Amisulpride-treated patients showed reduced platelet glutamate-response. This cannot be explained by a direct inhibitory effect of amisulpride. However, further studies are necessary to clarify whether the observed hypoglutamergic platelet function is a treatment-effect or endogeneous to the disorder.