Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine

Frank R Sharp, M. Butman, S. Wang, J. Koistinaho, S. H. Graham, S. M. Sagar, L. Noble, P. Berger, F. M. Longo

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

The 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.

Original languageEnglish (US)
Pages (from-to)605-616
Number of pages12
JournalJournal of Neuroscience Research
Volume33
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • cingulate cortex
  • dopamine receptors
  • glutamate
  • heat shock proteins
  • ketamine
  • MK801
  • neuronal injury
  • NMDA antagonists
  • NMDA receptors
  • phencyclidine (PCP)
  • psychosis
  • schizophrenia
  • sigma receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine'. Together they form a unique fingerprint.

  • Cite this