Studies on dopaminergic and GABAergic markers in striatum reveals a decrease in the dopamine transporter in schizophrenia.
Changes in the interaction between dopaminergic and GABAergic systems in the striatum have been suggested to be important in the pathology of schizophrenia. If that hypothesis is correct, these changes could produce inter-related changes in the dopaminergic and GABAergic systems in the striatum from schizophrenic subjects. To test this proposition we measured important markers on dopaminergic and GABAergic neurons in striatum obtained post-mortem from schizophrenic and non-schizophrenic subjects. There was a significant decrease in the density of the dopamine transporter (mean+/-SEM: 230+/-31 vs. 334+/-22fmol/mg ETE; P=0.01), but not nitric oxide synthase, dopamine D(2)-like, D(1)-like, D(3) or GABA(A) receptors in subjects with schizophrenia. There were no inter-related changes in the dopaminergic or GABAergic markers. In the schizophrenic subjects, the density of dopamine D(1)-like receptors decreased with age and was positively correlated with the density of dopamine D(2)-like receptors. This study does not readily add weight to the hypothesis that changes in the interaction between dopamine and GABA in the striatum are important in the pathology of schizophrenia. However, our findings could indicate that changes in the dopamine transporter within the striatum, either because of decreased transporter numbers per se or as a result of innervating neuronal loss, may be involved in the pathology of the illness.
Dean
B
B
The Rebecca Cooper Research Laboratories, The Division of Molecular Schizophrenia, The Mental Health Research Institute, Victoria, 3052, Parkville, Australia. b.dean@papyrus.mhri.edu.au
Hussain
T
T
D000328:Adult; D003342:Corpus Striatum / Q000473:pathology*; D004298:Dopamine / Q000032:analysis*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000032:analysis*; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000473:pathology; D011954:Receptors, Dopamine / Q000032:analysis; D018079:Receptors, GABA / Q000032:analysis; D012559:Schizophrenia / Q000473:pathology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D004298:Dopamine