Ceruletide suppresses endogenous dopamine release via vagal afferent system, studied by in vivo intracerebral dialysis.

Ceruletide, a cholecystokinin-related decapeptide, has been reported to have some therapeutic effects on tardive dyskinesia and other involuntary movement disorders. In order to clarify the effects of ceruletide on dopaminergic activity in the rat striatum, we measured the release of endogenous dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) after intraperitoneal administration of ceruletide (2, 20, 200 micrograms/kg) using in vivo intracerebral dialysis techniques. After administration of ceruletide (200 micrograms/kg), extracellular DA decreased significantly (P less than 0.05) for 0.5-3 h. The maximal reduction of extracellular DA (by 29%) was observed for 2-2.5 h. Extracellular DA was reduced (21%) by 20 but not by 2 micrograms/kg ceruletide. DOPAC and HVA did not change at any dose of ceruletide. We also demonstrated that bilateral subdiaphragmatic vagotomy blocked this inhibitory effect of ceruletide on DA release. These findings indicate that peripherally administered ceruletide suppresses endogenous DA release via the vagal afferent system.