Ceruletide, a cholecystokinin-like decapeptide, differentially reduces the stimulant effect of MK-801 and ketamine: evaluation by discrete shuttle avoidance in mice.
H Kuribara
European Journal of Pharmacology January 26, 1993 DOI: 10.1016/0014-2999(93)90677-a (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice trained to discrete shuttle avoidance |
| Interventions | Ketamine Methamphetamine Ceruletide Haloperidol |
| Dose | MK-801 0.03-0.3 mg/kg i.p.; ketamine 1-20 mg/kg s.c.; methamphetamine 0.1-1 mg/kg s.c.; ceruletide 0.1-10 micrograms/kg s.c.; haloperidol 0.01-0.1 mg/kg s.c. |
| Topics | Esketamine Ketamine |
| Key findings | MK-801, ketamine and methamphetamine all dose-dependently increased avoidance response rate, with roughly equipotent effects at 0.1 mg/kg, 10 mg/kg and 0.3 mg/kg respectively. Ceruletide at 0.1 micrograms/kg, itself without significant effect, completely attenuated MK-801's response-increasing effect, whereas up to 10 micrograms/kg was needed to significantly reduce ketamine's and methamphetamine's effects. Haloperidol inhibited all three stimulants to a similar degree. The authors suggest low-dose ceruletide selectively inhibits MK-801's stimulant effect, possibly through reduced dopamine release in the nucleus accumbens. |
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 site in the nucleus accumbens may be mainly involved in this interaction.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 2
- The phencyclidine (PCP) analog N-[1-(2-benzo(B)thiophenyl) cyclohexyl]piperidine shares cocaine-like but not other characteristic behavioral effects with PCP, ketamine and MK-801. Journal of Pharmacology and Experimental Therapeutics September 1, 1989
- A comparison between classes of drugs having phencyclidine-like behavioral properties on dopamine efflux in vitro and dopamine metabolism in vivo. Journal of Pharmacology and Experimental Therapeutics November 1, 1984