Abstract
The drug sensitivity of synaptosomal high-affinity dopamine (DA) uptake was investigated in post-mortem brain regions of schizophrenics, in comparison to controls matched for age, sex, and post-mortem delay, and in model experiments in rats. DA uptake was inhibited by nomifensine in the investigated regions of rat brain in a concentration-dependent manner; the regional rank order of inhibitory potency was: nucleus (n) caudatus > n. accumbens > frontal cortex. Furthermore, it was shown that the inhibitory potency of nomifensine is unchanged afterin situ storage of rat brain tissue for 48 h and after the cryopreservation method used. In post-mortem brain of human controls, nomifensine inhibited DA uptake with the same regional differences as in rats; however, the inhibitory potencies were three-fourfold weaker. In schizophrenia, on the other hand, synaptosomal DA uptake inhibition by nomifensine was significantly weaker than in the corresponding control brains for all regions studied. This suggests a decreased affinity of the DA uptake carrier to nomifensine, similar to DA shown in recent studies with schizophrenic patients. The possible relevance of investigating functional parameters for understanding patho-biochemical mechanisms in schizophrenia is discussed.
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Hetey, L., Berg, R. & Schlesinger, T. Characterization of synaptosomal dopamine uptake in post-mortem brain regions of schizophrenics. Neurochemical Pathology 7, 221–232 (1987). https://doi.org/10.1007/BF03160182
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DOI: https://doi.org/10.1007/BF03160182