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 treatment with neuroleptics. To investigate if TD may be a result of neuroleptic-induced excessive stimulation of striatal glutamate receptors, the effect of the anti-excitotoxic GM1 ganglioside was studied in a rat model of TD. In an acute experiment each of four groups of rats was treated with GM1 20 mg/kg SC+saline IP, saline SC+haloperidol 1.2 mg/kg IP, GM1 SC+haloperidol IP, or saline SC+saline IP. In a subsequent long-term experiment lasting 16 weeks, each of the four groups was treated as in the acute experiment, with the exception that haloperidol was injected IM as decanoate 38 mg/kg every 4 weeks, and the controls received vehicle injections. The behavior was videotaped and scored at intervals during both experiments, including 16 weeks after cessation of the long-term treatment. Haloperidol induced a significant increase in vacuous chewing movements (VCM) and immobility both in the acute and in the long-term experiment. Other categories of behaviour (rearing, moving, sitting) were significantly affected only in the acute experiment. 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 weeks after cessation of the long-term treatment. These results suggest that long-lasting changes in striatal function induced by excessive glutamate receptor stimulation may be a mechanism for the development of VCM in rats and perhaps also for TD in humans.
Andreassen
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OA
Department of Physiology, Section Sandviken Hospital, University of Bergen, Norway.
Jørgensen
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HA
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D005677:G(M1) Ganglioside; D006220:Haloperidol