g(m1)-ganglioside and Dyskinesia--Drug-Induced

1- The effects of monosialoganglioside GM1 were studied on a new model of tardive dyskinesia, i.e., the frequency of spontaneous tongue protrusions in rats repeatedly treated with reserpine. 2- Rats were co-treated with vehicle (VEH) or reserpine (RES) (0.1 mg/kg, s.c., every other day) and saline (SAL) or GM1 (5 mg/kg, i.p., every day) for 30 days and observed for tongue protrusions on days 10, 20 and 30. 3- During each test day animals of the RES + SAL group exhibited an increase in tongue protrusions relative to rats of the VEH + SAL group. However, rats of the RES + GM1 group showed an increased frequency of tongue protrusions only on day 10, when compared to animals of the VEH + SAL group. There were no significant differences in tongue protrusion frequency between the VEH + GM1 and the VEH + SAL groups. 4- These results differ from previous studies which reported a facilitatory effect of GM1 co-administration on conventional behavioral animal models of tardive dyskinesia. The possibility is raised that GM1 attenuates the reserpine-induced increase in tongue protrusions through its protective effect on glutamate/oxidative stress neurotoxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipsychotic Agents; Disease Models, Animal; Dyskinesia, Drug-Induced; Free Radicals; G(M1) Ganglioside; Male; Motor Activity; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Receptors, Dopamine; Reserpine; Tongue

Injection of a dose of haloperidol that has no obvious behavioral effects in normal mice, produces akinesia, catalepsy, and sensory neglect in MPTP-treated mice. Chronic GM1 ganglioside administration improves the behavioral impairments, partially restores striatal dopamine (DA) content and prevents DA D-2 receptor up-regulation. Discontinuation of GM1 ganglioside treatment results in a time-dependent decline of striatal DA content to pretreatment pathological levels, return of haloperidol-induced sensorimotor deficits and a rise of DA D-2 receptor density in the striatum. Apparently, continuous administration of GM1 ganglioside is necessary to maintain the biochemical and behavioral recovery in the MPTP-treated mouse. These observations may provide useful cues for understanding the mechanism of action of GM1 ganglioside.

Topics: Animals; Brain Diseases; Catalepsy; Corpus Striatum; Dopamine; Dyskinesia, Drug-Induced; G(M1) Ganglioside; Haloperidol; Injections, Intravenous; Male; Mice; Motor Activity; Movement Disorders; MPTP Poisoning; Orientation; Receptors, Dopamine; Receptors, Dopamine D2; Up-Regulation