Effect of ceruletide on discriminated avoidance behavior in rats.

To clarify the central action of peripherally administered ceruletide, we examined the effects of ceruletide and four different classes of neuroleptics, i.e. haloperidol, chlorpromazine, oxypertine and sulpiride, on the discriminated avoidance response (DAR) in rats. Ceruletide and sulpiride did not suppress the DAR over a broad range of doses, whereas other three neuroleptics caused a dose-related decrease in both avoidance and response rates. In addition, the combined administration of ceruletide (100 micrograms/kg s.c.) and neuroleptics at critical doses that suppress the DAR caused a significant reduction in the avoidance rate without affecting the response rate, compared with neuroleptics alone. These findings suggest that ceruletide influences the central dopaminergic system, potentiating the central effects of neuroleptics and producing the favorable therapeutic effects observed in the clinical trials.