Ganglioside interactions with the dopaminergic system of rats.

Abstract

The effects of ganglioside treatment on changes in dopaminergic function following 6-hydroxydopamine (6-OHDA) or repeated exposure to haloperidol were studied in male Fischer-344 rats. Rats were injected sc with 30 mg/kg of a mixed ganglioside preparation (GM) at the time of the surgery and for 13 days after receiving an intranigral injection of 6-OHDA. GM treatment attenuated 6-OHDA depletion of striatal dopamine (DA) and DOPAC. Another group of rats was implanted with chronic indwelling cannulas in the lateral cerebroventricles at the time of 6-OHDA administration into the substantia nigra. Daily intraventricular injection of 25 or 50 micrograms GM attenuated depletions of striatal DA and DOPAC. A separate experiment sought to determine the effects of GM1 on the development of receptor supersensitivity produced by repeated exposure to a dopamine receptor antagonist. Rats were injected sc with 1 mg/kg haloperidol for 8 or for 16 days; some rats were coadministered 20 mg/kg GM1 sc. Four days after the last dose, the rats were challenged with 1 mg/kg apomorphine, and activity was counted for 60 min. Treatment with GM1 decreased the behavioral supersensitivity to apomorphine induced by repeated exposure to haloperidol. These experiments suggest that treatment with GM can have a protective effect against 6-OHDA-induced depletion of dopamine if treatment with GM begins at the time of lesioning. These studies also support receptor binding data from other laboratories indicating that treatment with GM1 can affect up-regulation of dopamine receptors.