Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine
FR Sharp, M. Butman, S. Wang, Jari Koıstınaho, S. H. Graham, S. M. Sagar, L. Noble, P. Berger, F. M. Longo
Journal of Neuroscience Research December 1, 1992 DOI: 10.1002/jnr.490330413 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | PCP MK801 ketamine haloperidol rimcazole |
| Dose | PCP ≥5 mg/kg, MK801 ≥0.1 mg/kg, ketamine >20 mg/kg |
| Topics | Esketamine Ketamine |
| Key findings | PCP, MK801, and ketamine induce hsp70 in injured neurons of the posterior cingulate and retrosplenial cortex in rats aged 30 days or older, and this injury is prevented by haloperidol and rimcazole. |
Abstract
AbstractThe non‐competitive NMDA receptor antagonists, PCP (phencyclidine), MK801, and ketamine produce psychosis in humans and abnormal vacuoles in posterior cingulate and retrosplenial rat cortical neurons. We show that PCP (≥5 mg/kg), MK801 (≥0.1 mg/kg), and ketamine (>20 mg/kg) induce hsp70 mRNA and HSP70 heat shock protein in these vacuolated, injured neurons, and PCP also induces hsp70 in injured neocortical, piriform, and amygdala neurons. The PCP, MK801, and ketamine drug induced injury occurs in 30 day and older rats, but not in 0–20 day old rats, and is prevented by prior administration of the antipsychotic drugs haloperidol and rimcazole. Since haloperidol and rimcazole block dopamine and sigma receptors, and since M1 muscarinic cholinergic receptor antagonists also prevent the injury produced by PCP, MK801, and ketamine, future studies will be needed to determine whether dopamine, sigma, M1, or other receptors mediate the injury. © 1992 Wiley‐Liss, Inc.
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 12
- NMDA receptor regulation of memory and behavior in humans Hippocampus October 1, 2001
- Halothane and Diazepam Inhibit Ketamine-induced c-fos Expression in the Rat Cingulate Cortex Anesthesiology October 1, 1996
- Expression of heat shock protein HSP-70 in the retrosplenial cortex of rat brain after administration of (R,S)-ketamine and (S)-ketamine, but not (R)-ketamine. Pharmacology, Biochemistry, and Behavior September 2018
- Distinct retrosplenial cortex cell populations and their spike dynamics during ketamine-induced unconscious state PLoS One October 26, 2017
- The NMDA receptor hypofunction model of psychosis. Annals of the New York Academy of Sciences November 1, 2003
and 7 more in the library
Cites 5
- NMDA Antagonist Neurotoxicity: Mechanism and Prevention Science December 6, 1991
- Degenerative and axon outgrowth-altering effects of phencyclidine in human fetal cerebral cortical cells. Neuropharmacology March 1992
- Different modulation of the binding to two phencyclidine (PCP) receptor subtypes: effects of N-methyl-D-aspartate agonists and antagonists. Neuroscience Letters October 9, 1989
- Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science June 16, 1989
- MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics June 1, 1988