Ceruletide, a cholecystokinin-like decapeptide, differentially reduces the stimulant effect of MK-801 and ketamine: evaluation by discrete shuttle avoidance in mice.
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 site in the nucleus accumbens may be mainly involved in this interaction.
Kuribara
H
H
Division for Behavior Analysis, Gunma University School of Medicine, Maebashi, Japan.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D007649:Ketamine; D016291:Dizocilpine Maleate; D002108:Ceruletide