The effects of repeated administrations of MK-801 on ERK and GSK-3β signalling pathways in the rat frontal cortex

Myoung Suk Seo, Se Hyun Kim, Yong Min Ahn, Yeni Kim, Won Je Jeon, Se Chang Yoon, Myoung Sun Roh, Yong Sung Juhnn, Yong Sik Kim

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Repeated administrations of NMDA receptor antagonists induce behavioural changes which resemble the symptoms of schizophrenia in animals. ERK and GSK-3β associated signalling pathways have been implicated in the pathogenesis of psychosis and in the action mechanisms of various psychotropic agents. Here, we observed the phosphorylations of ERK and GSK-3β and related molecules in the rat frontal cortex after repeated intraperitoneal injections of MK-801, over periods of 1, 5, and 10 d. Repeated treatment with 0.5, 1, and 2 mg/kg MK-801 increased the phosphorylation levels of the MEK-ERK-p90RSK and Akt-GSK-3β pathways and concomitantly and significantly increased CREB phosphorylation in the rat frontal cortex. However, single MK-801 treatment did not induce these significant changes. In addition, the immunoreactivities of HSP72, Bax, and PARP were not altered, which suggests that neuronal damage may not occur in the rat frontal cortex in response to chronic MK-801 treatment. These findings suggest that chronic exposure to MK-801 may induce pro-survival and anti-apoptotic activity without significant neuronal damage in the rat frontal cortex. Moreover, this adaptive change might be associated with the psychotomimetic action of MK-801.

Original languageEnglish
Pages (from-to)359-368
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume10
Issue number3
DOIs
StatePublished - Jun 2007

Keywords

  • Akt
  • CREB
  • MAPK
  • NMDA receptor antagonist
  • Psychotomimetics

Fingerprint

Dive into the research topics of 'The effects of repeated administrations of MK-801 on ERK and GSK-3β signalling pathways in the rat frontal cortex'. Together they form a unique fingerprint.

Cite this