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 th e striatum have been suggested to be important in the pathology of schizoph renia. If that hypothesis is correct, these changes could produce inter-rel ated changes in the dopaminergic and GABAergic systems in the striatum from schizophrenic subjects. To test this proposition we measured important mar kers on dopaminergic and GABAergic neurons in striatum obtained post-mortem from schizophrenic and nonschizophrenic subjects. There was a significant decrease in the density of the dopamine transporter (mean SEM: 230 +/- 31 v s. 334 +/- 22 fmol/mg ETE; P = 0.01), but not nitric oxide synthase, dopami ne D-2-like, D-1-like, D-3 or GABA(A) receptors in subjects with schizophre nia. There were no inter-related changes in the dopaminergic or GABAergic m arkers. In the schizophrenic subjects, the density of dopamine D-1-like rec eptors 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 th e striatum are important in the pathology of schizophrenia. However, our fi ndings could indicate that changes in the dopamine transporter within the s triatum, either because of decreased transporter numbers per se or as a res ult of innervating neuronal loss, may be involved in the pathology of the i llness. (C) 2001 Elsevier Science B.V. All rights reserved.