The effects of MK-801 on the phosphorylation of Ser338-c-Raf-MEK-ERK pathway in the rat frontal cortex.
MK-801 induces psychotomimetic behavioural changes in animals. ERKs play an important role in the pathogenesis of schizophrenia and in the action of antipsychotics and psychotomimetics. We observed phosphorylation of ERK-signalling-pathway-associated molecules in the rat frontal cortex and their association with rat behaviour after MK-801 administration. After injecting 0.25-1 mg/kg MK-801, ERK phosphorylation decreased compared to vehicle treatment, and rats showed increased locomotion. After 2 mg/kg treatment, ERK phosphorylation increased and rat motility started to decrease. After treating with 4-8 mg/kg, ERK phosphorylation once again decreased and rats showed hypomotility and ataxia. ERK phosphorylation levels were maintained from 15 min to 90 min after 1 or 2 mg/kg treatment. Ser338-c-Raf and MEK phosphorylation showed similar dose-dependent and temporal patterns to those of ERK. Taken together, Ser338-c-Raf-MEK-ERK phosphorylation by MK-801 in the rat frontal cortex showed a specific pattern and may be associated with behavioural changes induced by MK-801.
Ahn
Yong Min
YM
Department of Psychiatry and Behavioural Science and Institute of Human Behavioural Medicine, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-Gu, Seoul 110-799, Korea.
Seo
Myoung Suk
MS
Kim
Se Hyun
SH
Kim
Yeni
Y
Juhnn
Yong-Sung
YS
Kim
Yong Sik
YS
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D016291:Dizocilpine Maleate; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases