EFFECTS OF CERULETIDE ON PERIORAL MOVEMENTS AND THE DOPAMINE RECEPTOR-ADENYLATE CYCLASE SYSTEM IN RATS CHRONICALLY TREATED WITH FLUPHENAZINE

The effects of repeated administration of ceruletide (100 mu g/kg/perd ay, IP for 3 days) on perioral movements and the striatal dopamine rec eptor adenylate cyclase system were examined in rats chronically treat ed with fluphenazine enanthate (FPZ) (25 mg/kg IM every 3 weeks for 30 weeks) and sesame oil-treated (control) rats. After the tenth injecti on of fluphenazine, the rats started to display five types of perioral movements (teeth chattering, chewing, tongue protrusion, mouth openin g and perioral tremors). Moreover, increases in SCH23390 binding and s piperone binding to striatal membranes were found in the FPZ-treated r ats. Furthermore, dopamine receptor-coupled adenylate cyclase activity was potentiated in striatal membranes. High amplitude EMG discharges (8-10 Hz), recorded from the masseter in the FPZ-treated rats occurred concurrently with perioral tremors. Repeated ceruletide (CLT) injecti ons abolished perioral movements, and reversed both the elevated SCH23 390 binding and the dopamine stimulated adenylate cyclase (AC) activit y to the control level, The effect of CLT on perioral movements, D-1 r eceptors and dopamine-stimulated AC activity continued for 6 days afte r the final CLT injection. These findings suggest that systemically ad ministered CLT affects the D-1 receptor adenylate cyclase system and t hat an increase of the D-1 receptor mechanism may play an important ro le in the pathogenesis of tardive dyskinesia.