HIGH-FREQUENCY ORAL MOVEMENTS INDUCED BY LONG-TERM ADMINISTRATION OF AMPEROZIDE BUT NOT FG5803 IN RATS

Long-term studies of antipsychotic-induced oral movements may serve as a rat model of acute and tardive movement disorders. Vacuous chewing movements (VCM), tongue protrusions (TP), and jaw tremors (TR) were st udied in rats during acute and chronic administration of two potential antipsychotics, amperozide and FG5803. Comparisons were made with hal operidol and vehicle. Single intraperitoneal injections of amperozide (0.2, 1, or 5 mg/kg) or FG5803 (1.2, 6, or 30 mg/kg) were without effe ct on oral behaviors. During long-term drug administration, withdrawal and readministration, endpoint analysis was focused on changes in sup ranormal oral movements. The maximal mean control frequencies found at 29 sessions during 14 months experiment +2 standard deviations were u sed to define the upper limit of the normal range. FG5803 (1.2, 6, or 30 mg/kg per day) administered via the drinking water for 12 months, d id not produce significant deviations from this normal range with resp ect to VCM, TP, or TR, and this drug was not studied further. Rats rec eiving amperozide (0.2, 1, or 5 mg/kg per day) showed dose-related inc reases in oral movements over the year. The changes began after 3 mont hs of treatment with amperozide 1 and 5 mg/kg per day, but became stat istically significant only during the second half of the treatment yea r. Amperozide 0.2 mg/kg per day did not produce significant changes in oral movements during administration for a year, but drug withdrawal resulted in a significant rise in TP behavior. Haloperidol (1 mg/kg pe r day) produced increases in supranormal oral movements which tended t o level out after 9 months. In all groups with significant elevations (i.e. haloperidol and amperozide 1 and 5 mg/kg per day), there was a p ersistence of such movements during a month of drug withdrawal. During treatment with amperozide (1 or 5 mg/kg per day), some rats developed a high frequency chewing behavior up to 175 VCMs/min. It is concluded that long-term treatment with amperozide, but not FG5803, produced a tardive pattern of supranormal oral movements. The importance of these findings for the clinical future of amperozide is difficult to predic t, due to the unexpected finding of high-frequency chewing, which has not been noticed before during extensive studies of classical neurolep tics.