THE ROLE OF STRIATAL GLUTAMATERGIC SYSTEM IN HALOPERIDOL-INDUCED DOPAMINE-RECEPTOR SUPERSENSITIVITY AND EFFECTS OF MONOSIALOGANGLIOSIDE GM1

The mechanism underlying the action of ganglioside GM1 on the increase of haloperidol-induced dopamine receptor supersensitivity was studied using the method of chemically stimulated (H-3)-D-aspartate release i n rat striatal slices. After a 3-week chronic haloperidol treatment th e transmitter release was reduced by about 30%, with a further reducti on to 40% when GM1 was applied chronically as well. This suggests that the downregulation of the glutamatergic system by chronic haloperidol treatment is potentiated by gangliosides. The acute effect of ganglio sides on the stimulated (H-3)-D-aspartate release from striatal slices was tested by adding GM1 to the superfusion medium. When given at a c oncentration of 10(-4) M, GM1 did not after the amino acid release its elf. GM1 did, however, reduce the haloperidol-enhanced (H-3)-D-asparta te release to control levers and elevated the glutamate-stimulated (H- 3)-D-aspartate release. Binding experiments indicate that gangliosides do not directly interact with glutamate or dopamine receptors. The da ta are discussed in view of earlier findings that GM1 potentiates the behavioral supersensitivity following chronic haloperidol treatment wi thout directly altering dopamine receptor supersensitivity. (C) 1997 E lsevier Science Inc.