DNQX inhibits phencyclidine (PCP) and ketamine induction of the hsp70 heat shock gene in the rat cingulate and retrosplenial cortex.
J W Sharp, D L Petersen, M T Langford
Brain Research July 31, 1995 DOI: 10.1016/0006-8993(95)00477-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rats (specific strain and number not stated) |
| Interventions | DNQX Phencyclidine (PCP) Ketamine |
| Dose | DNQX 5 mg/kg or 10 mg/kg intraperitoneal, or 5 microliters of 0.5 mg/ml intraventricular; PCP 40 mg/kg; ketamine 80, 100, 120 mg/kg |
| Measures | hsp70 induction in the posterior cingulate and retrosplenial cortex |
| Topics | Esketamine Ketamine |
| Key findings | DNQX, an AMPA receptor antagonist, significantly reduced hsp70 induction in the posterior cingulate and retrosplenial cortex caused by PCP (40 mg/kg) and ketamine (80, 100, 120 mg/kg) in rats, with the intraventricular dose producing the largest decrease. The authors conclude that AMPA receptors play a role in PCP/ketamine induction of hsp70, likely by preventing excess calcium influx through voltage-gated calcium channels. |
Abstract
Phencyclidine (PCP) and ketamine are known to block NMDA receptor mediated excitotoxicity by non-competitively blocking the NMDA receptor calcium channel. PCP and ketamine have the paradoxical effect of also inducing the heat shock gene, hsp70, in the cingulate and retrosplenial cortex of the rat. The present study shows that DNQX, a specific AMPA receptor antagonist, given as either a 5 mg/kg or 10 mg/kg intraperitoneal dose or into the lateral cerebral ventricle (5 microliters of 0.5 mg/ml) significantly diminished PCP (40 mg/kg) and ketamine (80, 100, 120 mg/kg) hsp70 induction in the posterior cingulate and retrosplenial cortex. The most dramatic decrease of hsp70 induction was seen with the intraventricular dose of DNQX. Present findings show that the AMPA receptor has a role in PCP/ketamine induction of hsp70 in the cortex. DNQX inhibition of PCP/ketamine hsp70 induction was likely related to AMPA receptor antagonism which prevented excess calcium influx via voltage-gated calcium channels.
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 7
- 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 Journal of Neuroscience April 15, 1997
- NMDA receptor regulation of memory and behavior in humans Hippocampus October 1, 2001
- Modafinil reverses phencyclidine-induced deficits in cognitive flexibility, cerebral metabolism, and functional brain connectivity. Schizophrenia Bulletin September 1, 2010
- The NMDA receptor hypofunction model of psychosis. Annals of the New York Academy of Sciences November 1, 2003
- Psychosis: pathological activation of limbic thalamocortical circuits by psychomimetics and schizophrenia? Trends in Neurosciences June 1, 2001
and 2 more in the library
Cites 4
- NMDA Antagonist Neurotoxicity: Mechanism and Prevention Science December 6, 1991
- Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine Journal of Neuroscience Research December 1, 1992
- Degenerative and axon outgrowth-altering effects of phencyclidine in human fetal cerebral cortical cells. Neuropharmacology March 1992
- 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