Haloperidol prevents ketamine- and phencyclidine-induced HSP70 protein expression but not microglial activation

Riitta Näkki, Jeremy Nickolenko, Jaymin Chang, Stephen M. Sagar, Frank R Sharp

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, including ketamine and phencyclidine (PCP), produce abnormal intracellular vacuoles in posterior cingulate and retrosplenial cortical neurons in the rat. Ketamine also induces 70-kDa heat shock protein (HSP70) expression in pyramidal neurons in the posterior cingulate and retrosplenial cortex and, as shown by this study, activates microglia in the retrosplenial cortex of the rat. Whereas HSP70 protein expression was induced with ketamine doses of 40 mg/kg tip) and higher, doses of 80 mg/kg and higher were required to activate microglia. HSP70-positive neurons were observed in 30- to 90-day-old rats but not in younger, 10- to 20-day-old animals following ketamine (80 mg/kg, ip). Pretreatment with the antipsychotic drug haloperidol at doses of 1.0 mg/kg and above abolished all HSP70 immunostaining produced by ketamine (80 mg/kg). However, a single dose of haloperidol (5 mg/kg, im) did not decrease the number of microglia activated in retrosplenial cortex by ketamine (80-140 mg/kg). Similarly, PCP (10 and 50 mg/kg, ip)-induced microglial activation in the posterior cingulate and retrosplenial cortex of adult rats was nest blocked by haloperidol (10 mg/kg, im, 1 h prior to PCP). These results suggest that ketamine and PCP injure neurons in the posterior cingulate and retrosplenial cortex of adult rats. Though haloperidol may afford some protection against this injury since it inhibits induction of HSP70 expression, the failure to prevent microglial activation suggests that single doses of haloperidol do not completely protect neurons from NMDA antagonist toxicity.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalExperimental Neurology
Volume137
Issue number2
DOIs
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

Phencyclidine
Ketamine
Haloperidol
Gyrus Cinguli
Microglia
Proteins
Neurons
HSP70 Heat-Shock Proteins
Pyramidal Cells
N-Methylaspartate
Vacuoles
N-Methyl-D-Aspartate Receptors
Antipsychotic Agents
Wounds and Injuries

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Haloperidol prevents ketamine- and phencyclidine-induced HSP70 protein expression but not microglial activation. / Näkki, Riitta; Nickolenko, Jeremy; Chang, Jaymin; Sagar, Stephen M.; Sharp, Frank R.

In: Experimental Neurology, Vol. 137, No. 2, 02.1996, p. 234-241.

Research output: Contribution to journalArticle

Näkki, Riitta ; Nickolenko, Jeremy ; Chang, Jaymin ; Sagar, Stephen M. ; Sharp, Frank R. / Haloperidol prevents ketamine- and phencyclidine-induced HSP70 protein expression but not microglial activation. In: Experimental Neurology. 1996 ; Vol. 137, No. 2. pp. 234-241.
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