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 (3H)-D-aspartate release in rat striatal slices. After a 3-week chronic haloperidol treatment the transmitter release was reduced by about 30%, with a further reduction 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 gangliosides on the stimulated (3H)-D-aspartate release from striatal slices was tested by adding GM1 to the superfusion medium. When given at a concentration of 10(-4) M, GM1 did not alter the amino acid release itself. GM1 did, however, reduce the haloperidol-enhanced (3H)-D-aspartate release to control levels and elevated the glutamate-stimulated (3H)-D-aspartate release. Binding experiments indicate that gangliosides do not directly interact with glutamate or dopamine receptors. The data are discussed in view of earlier findings that GM1 potentiates the behavioral supersensitivity following chronic haloperidol treatment without directly altering dopamine receptor supersensitivity.
Schroeder
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Institute of Pharmacology and Toxicology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Schroeder
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D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D001224:Aspartic Acid; D005677:G(M1) Ganglioside; D018698:Glutamic Acid; D013134:Spiperone; D006220:Haloperidol