Characterization of synaptosomal dopamine uptake in post-mortem brain regions of schizophrenics.
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 greater than n. accumbens greater than frontal cortex. Furthermore, it was shown that the inhibitory potency of nomifensine is unchanged after in 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.
Hetey
L
L
Institute of Pharmacology and Toxicology of Charité, Humboldt University Berlin, GDR.
Berg
R
R
Schlesinger
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005615:Freezing; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D011309:Preservation, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D013574:Synaptosomes / Q000378:metabolism*
D018492:Dopamine Antagonists; D009627:Nomifensine; D004298:Dopamine