Fluoxetine prevents PCP- and MK801-induced HSP70 expression in injured limbic cortical neurons of rats

Midori Tomitaka, Shinichiro Tomitaka, Sunita Rajdev, Frank R Sharp

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: N-Methyl-D-aspartate (NMDA) receptor antagonists, including phencyclidine (PCP) and dizocilpine (MK801), cause schizophrenialike psychosis in humans, and produce vacuolated neurons in the cingulate and retrosplenial cortices of the rat brain. Since psychotically depressed patients and schizophrenic depressed patients may require treatment with selective serotonin reuptake inhibitors (SSRIs), it is of interest to examine the relationship between SSRIs and NMDA antagonist neurotoxicity. Methods: The neurotoxicity of PCP and MK801 was assessed using heat shock protein (HSP70) immunocytochemistry and HSP70 Western blots because HSP70 is expressed in the injured, vacuolated neurons. Female rats were given fluoxetine (0, 5, 10, and 20 mg/kg IP) followed 1 hour later by MK801 (1 mg/kg IP) or PCP (50 mg/kg IP). Results: Pretreatment with fluoxetine (20 mg/kg IP) 1 hour before MK801 prevented the induction of HSP70 by MK801 in the cingulate and retrosplenial cortices. Pretreatment with fluoxetine (10 or 20 mg/kg IP) 1 hour before PCP also prevented the HSP70 induction by PCP. Conclusions: Fluoxetine prevents the neurotoxicity of NMDA receptor antagonists in rat brain. This suggests the possibility that SSRIs could modulate psychosis, and may provide a model for examining the link between the hallucinogenic properties of PCP and lysergic acid diethylamide. (C) 2000 Society of Biological Psychiatry.

Original languageEnglish (US)
Pages (from-to)836-841
Number of pages6
JournalBiological Psychiatry
Volume47
Issue number9
DOIs
StatePublished - May 1 2000
Externally publishedYes

Fingerprint

Fluoxetine
Serotonin Uptake Inhibitors
Neurons
Gyrus Cinguli
N-Methyl-D-Aspartate Receptors
Psychotic Disorders
Phencyclidine
Lysergic Acid Diethylamide
HSP70 Heat-Shock Proteins
Dizocilpine Maleate
Brain
N-Methylaspartate
Western Blotting
Immunohistochemistry
Therapeutics

Keywords

  • Dizocilpine
  • Fluoxetine
  • LSD
  • MK801
  • PCP
  • Phencyclidine
  • Schizophrenia
  • Serotonin

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Fluoxetine prevents PCP- and MK801-induced HSP70 expression in injured limbic cortical neurons of rats. / Tomitaka, Midori; Tomitaka, Shinichiro; Rajdev, Sunita; Sharp, Frank R.

In: Biological Psychiatry, Vol. 47, No. 9, 01.05.2000, p. 836-841.

Research output: Contribution to journalArticle

Tomitaka, Midori ; Tomitaka, Shinichiro ; Rajdev, Sunita ; Sharp, Frank R. / Fluoxetine prevents PCP- and MK801-induced HSP70 expression in injured limbic cortical neurons of rats. In: Biological Psychiatry. 2000 ; Vol. 47, No. 9. pp. 836-841.
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AB - Background: N-Methyl-D-aspartate (NMDA) receptor antagonists, including phencyclidine (PCP) and dizocilpine (MK801), cause schizophrenialike psychosis in humans, and produce vacuolated neurons in the cingulate and retrosplenial cortices of the rat brain. Since psychotically depressed patients and schizophrenic depressed patients may require treatment with selective serotonin reuptake inhibitors (SSRIs), it is of interest to examine the relationship between SSRIs and NMDA antagonist neurotoxicity. Methods: The neurotoxicity of PCP and MK801 was assessed using heat shock protein (HSP70) immunocytochemistry and HSP70 Western blots because HSP70 is expressed in the injured, vacuolated neurons. Female rats were given fluoxetine (0, 5, 10, and 20 mg/kg IP) followed 1 hour later by MK801 (1 mg/kg IP) or PCP (50 mg/kg IP). Results: Pretreatment with fluoxetine (20 mg/kg IP) 1 hour before MK801 prevented the induction of HSP70 by MK801 in the cingulate and retrosplenial cortices. Pretreatment with fluoxetine (10 or 20 mg/kg IP) 1 hour before PCP also prevented the HSP70 induction by PCP. Conclusions: Fluoxetine prevents the neurotoxicity of NMDA receptor antagonists in rat brain. This suggests the possibility that SSRIs could modulate psychosis, and may provide a model for examining the link between the hallucinogenic properties of PCP and lysergic acid diethylamide. (C) 2000 Society of Biological Psychiatry.

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