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.