EFFECTS OF CERULETIDE ON THE DOPAMINE RECEPTOR-ADENYLATE CYCLASE SYSTEM IN STRIATUM AND FRONTAL-CORTEX OF RATS CHRONICALLY TREATED WITH HALOPERIDOL

Chronic treatment of rats with haloperidol decanoate (30 mg//kg and 100 mg/kg IM every 4 weeks for 52 weeks) increased [H-3] SCH 23390 binding in striatal membranes by 25% and 50% and in frontal cortical membranes by 56% and 125% in 30 and 100 mg/kg haloperidol treatment groups, respectively. These increases in [H-3] SCH 23390 binding to the membranes were restored to control levels after ceruletide treatment (100 mug/kg IP twice a day for 5 days). [H-3] Spiperone binding to the rat striatal and cortical membranes also increased after chronic haloperidol treatment (by 66% and 99% in striatal membranes and by 27% and 62% in cortical membranes in the 30 and 100 mg/kg haloperidol treatment groups, respectively). Administration of ceruletide to haloperidol-treated rats reduced the increased [H-3] spiperone binding to the cortical membranes toward the control level, but ceruletide was not effective in reducing the haloperidol-induced increase of [H-3] spiperone binding to the striatal membranes. Activation of adenylate cyclase by dopamine (1 muM or 100 muM) or Gpp(NH)p (1 muM) was reduced in striatal and cortical membranes from haloperidol-treated rats. Ceruletide restored the lowered level of dopamine-stimulated or Gpp(NH)p-stimulated adenylate cyclase activity in the membranes from haloperidol-treated rats to control levels. These findings indicate that systemically administered ceruletide is capable of reversing alterations in D1 dopamine receptor/D1 dopamine receptor coupling to adenylate cyclase in striatum and frontal cortex induced by chronic treatment of rats with haloperidol decanoate.