Gabaminergic and serotonergic modulation of the antidyskinetic effects of tiapride and oxiperomide in the model using 2-(N,N-dipropyl)animo-5,6-dihydroxytetralin.

The activities of oxiperomide and tiapride were compared with those of control "neuroleptic" agents in the dyskinesia model using 2-(N,N-dipropyl)amino-5,6-dihydroxytetralin to induce peri-oral movements, in order to determine whether the differential activities (oxiperomide and tiapride being comparatively more effective as antagonists) may involve striatal gabaminergic and serotonergic mechanisms. The peri-oral movements induced by the 2-aminotetralin compound (0.05 mg/kg s.c.) were antagonised by intrastriatal GABA (2.5--10 microgram bilateral) and serotonin (25--100 microgram bilateral). Sodium valproate (i.p.) had little effect but 1.25 mg/kg s.c. quipazine abolished the peri-oral dyskinesia. Subthreshold doses (i.p.) of oxiperomide and tiapride synergised with subthreshold intrastriatal doses of both GABA and serotonin, and with s.c. quipazine, to antagonise the peri-oral movements induced by the 2-aminotetralin compound. Subthreshold doses of haloperidol, sultopride, metoclopramide and pimozide failed to consistently antagonise peri-oral movements when similarly combined with GABA, serotonin or quipazine. It is suggested that, in addition to their known action on cerebral dopamine mechanisms, oxiperomide and tiapride may modify abnormal peri-oral movements by modulation of striatal gabaminergic and serotonergic mechanisms.