Ceruletide, a cholecystokinin-like decapeptide, differentially reduces the stimulant effect of MK-801 and ketamine: evaluation by discrete shuttle avoidance in mice

European Journal of Pharmacology
H Kuribara

Abstract

The non-competitive NMDA antagonist, MK-801 (dizocilpine: 0.03-0.3 mg/kg i.p.), a dissociative anesthetic, ketamine (1-20 mg/kg s.c.) and a CNS stimulant, methamphetamine (0.1-1 mg/kg s.c.), dose dependently increased the response rate in mice trained to discrete shuttle avoidance. MK-801 (0.1 mg/kg), ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg) were almost equipotent. The cholecystokinin-like decapeptide, ceruletide, 0.1 micrograms/kg s.c., completely attenuated the response-increasing effect of MK-801 (0.1 mg/kg), although at this dose ceruletide alone did not produce any significant change in the avoidance response. Up to 10 micrograms/kg of ceruletide, which itself decreased the response rate, was required to reduce significantly the response-increasing effect of ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg). On the other hand, haloperidol (0.01-0.1 mg/kg s.c.) decreased both the response rate and the % avoidance dose dependently, and inhibited the response-increasing effects of MK-801, ketamine and methamphetamine to almost the same degree. The present results suggest that comparatively lower doses of ceruletide inhibit selectively the stimulant effect of MK-801. Inhibition of dopamine release from the stored ...Continue Reading

References

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Citations

Jan 5, 2002·Journal of Basic and Clinical Physiology and Pharmacology·I Okulicz-KozarynK Kus

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