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Behavioral characteristics of ceruletide, a cholecystokinin-like decapeptide, were investigated by means of ambulatory activity in mice. Ceruletide at 100 and 300 micrograms/kg, i.p. slightly but significantly decreased the mouse's activity for 20 min. Therefore, 100 micrograms/kg of ceruletide was used in the experiment of combined administration with the central-acting drugs. Ceruletide reduced the increased activity which was produced by methamphetamine (2 mg/kg, s.c.), ephedrine (80 mg/kg, i.p.), methylphenidate (4 mg/kg, s.c.), cocaine (20 mg/kg, s.c.), mazindol (2.5 mg/kg, s.c.), apomorphine (0.5 mg/kg, s.c.), bromocriptine (8 mg/kg, i.p.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and morphine (20 mg/kg, s.c.) with different potencies and durations. The mice that had experienced ceruletide at 3 micrograms/kg for 5 times at intervals of 3-4 days demonstrated a significant increase in the sensitivity to methamphetamine, although the same treatment with 10-300 micrograms/kg of ceruletide was without effect. On the other hand, when 3-300 micrograms/kg of ceruletide was combined with 2 mg/kg of methamphetamine, the development of reverse tolerance to the ambulation-increasing effect of methamphetamine was inhibited dependently on the doses of ceruletide. However, the reverse tolerance to methamphetamine once established was scarcely modified by ceruletide when it was administered afterwards.

Characteristics of antagonism between ceruletide and various central-acting drugs: Investigation by means of ambulatory activity in mice.