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.
Wouter Koek, Françis C. Colpaert, James H Woods, J. Kamenka
Journal of Pharmacology and Experimental Therapeutics September 1, 1989 DOI: 10.1016/s0022-3565(25)22738-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Comparative behavioral pharmacology study in animals Peer reviewed |
|---|---|
| Population | Mice, rats, and pigeons |
| Interventions | BTCP PCP ketamine MK-801 cocaine haloperidol N-methyl-D-aspartate |
| Topics | Esketamine Ketamine |
| Key points | BTCP shared only cocaine-like behavioral effects with PCP, ketamine, and MK-801, and a dopamine antagonist reduced BTCP's effects, suggesting these effects may be mediated primarily by dopamine uptake mechanisms. In contrast, the authors propose that PCP receptors, not dopamine uptake, may mediate the cocaine-like effects of PCP, ketamine, and MK-801, since their potency order (MK-801 > PCP > ketamine) matches PCP receptor affinity but not dopamine uptake site affinity. |
Abstract
Phencyclidine (PCP) inhibits dopamine (DA) uptake and acts as a noncompetitive N-methyl-D-aspartate antagonist by binding to PCP receptors. The PCP analog N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine (BTCP, GK13) is a potent DA uptake inhibitor, but has low affinity for PCP receptors. The behavioral effects of BTCP were compared with those of PCP, ketamine, MK-801 and cocaine. In mice, BTCP, like cocaine, produced locomotion, sniffing and gnawing; haloperidol blocked these effects. PCP, ketamine and MK-801 produced locomotion, sniffing, swaying and falling. PCP, ketamine and MK-801 produced generalization in rats discriminating either cocaine, PCP or MK-801 from saline. Like cocaine, BTCP produced generalization in cocaine-discriminating rats only; haloperidol partially antagonized this effect. In pigeons, PCP-like catalepsy was produced by ketamine and MK-801, but not by BTCP. N-methyl-D-aspartate-induced convulsions in mice were antagonized by PCP, ketamine and MK-801, but not by BTCP or cocaine. Thus, BTCP shared only cocaine-like behavioral effects with PCP, ketamine and MK-801. A DA antagonist reduced the effects of BTCP. Therefore, the cocaine-like behavioral effects of BTCP may be mediated primarily by DA uptake mechanisms. However, PCP receptors, but not DA uptake mechanisms, may mediate the cocaine-like behavioral effects of PCP, ketamine and MK-801, because their order of potency in producing these effects (MK-801 greater than PCP greater than ketamine) is consistent with their potency order at PCP receptors, but not at DA uptake sites.
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
Cited by 9
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Synapse August 1, 2009
- The role of the hippocampo-prefrontal cortex system in phencyclidine-induced psychosis: a model for schizophrenia. Journal of physiology, Paris December 1, 2013
- The nonmedical use of ketamine, part two: A review of problem use and dependence. Journal of Psychoactive Drugs 2001
- The role of the NMDA synapse in general anesthesia. Toxicology Letters November 23, 1998
and 4 more in the library