Haloperidol-induced behavioral supersensitivity is increased by monosialoganglioside treatment in rats without...

In rats, dopamine supersensitivity was induced by haloperidol (HAL) treatment for 3 weeks, either by implanted polymer matrices or by daily i.p. injections (1.0 mg/kg/day). Thereafter, dopamine supersensitivity was tested by measurement of motor activity of the animals after application of the dopamine agonist apomorphine (0.5 mg/kg i.p.) and by determination of the specific D2 dopamine binding sites in the corpus striatum by using [3H]spiroperidol. In both modes of HAL administration, no differences were found in the behavioral and neurochemical parameters. The apomorphine-induced motility was enhanced, and the known up-regulation of the striatal D2 dopamine binding was detected. When monosialoganglioside (GM1) was given daily i.p. for 3 weeks parallel to HAL application, dopamine supersensitivity, as indicated by the apomorphine-induced motility, was enhanced significantly without affecting the striatal D2 dopamine receptor up-regulation. In a subsequent experiment, we reduced the HAL dose and observed the expected D2 dopamine up-regulation. However, GM1 had no effect either on striatal D2 dopamine binding or on motility. A thin-layer chromatography analysis revealed that the endogenous gangliosides pattern in the corpus striatum also remained unchanged after HAL treatment. In conclusion, GM1-induced elevation of behavioral supersensitivity cannot be explained by a direct interaction with the D2 dopamine receptor, but other mechanisms may be involved, such as the modification of second messenger pathways.