GM1 GANGLIOSIDE ATTENUATES THE DEVELOPMENT OF VACUOUS CHEWING MOVEMENTS INDUCED BY LONG-TERM HALOPERIDOL TREATMENT OF RATS

Tardive dyskinesia (TD) is a serious side-effect of long-term treatmen t with neuroleptics. To investigate if TD may be a result of neurolept ic-induced excessive stimulation of striatal glutamate receptors, the effect of the anti-excitotoxic GM1 ganglioside was studied in a rat mo del of TD. In an acute experiment each of four groups of rats was trea ted with GM1 20 mg/kg SC + saline IP, saline SC + haloperidol 1.2 mg/k g IP, GM1 SC + haloperidol IP, or saline SC + saline IP. In a subseque nt long-term experiment lasting 16 weeks, each of the four groups was treated as in the acute experiment, with the exception that haloperido l was injected IM as decanoate 38 mg/kg every 4 weeks, and the control s received vehicle injections. The behaviour was videotaped and scored at intervals during both experiments, including 16 weeks after cessat ion of the long-term treatment. Haloperidol induced a significant incr ease in vacuous chewing movements (VCM) and immobility both in the acu te and in the long-term experiment. Other categories of behaviour (rea ring, moving, sitting) were significantly affected only in the acute e xperiment. GM1 did not affect any of the acute behavioural effects of haloperidol, but significantly reduced VCM in the long-term experiment . The effects on VCM of haloperidol and GM1 persisted for at least 8 w eeks after cessation of the long-term treatment. These results suggest that long-lasting changes in striatal function induced by excessive g lutamate receptor stimulation may be a mechanism for the development o f VCM in rats and perhaps also for TD in humans.