The effects of MK-801 on the phosphorylation of Ser338-c-Raf-MEK-ERK pathway in the rat frontal cortex

• Published in: The international journal of neuropsychopharmacology 2006-08, Vol.9 (4), p.451-456
• Main Authors: Ahn, Yong Min, Seo, Myoung Suk, Kim, Se Hyun, Kim, Yeni, Juhnn, Yong-Sung, Kim, Yong Sik
• Format: Article
• Language: English
• Subjects: Animals; Brief Report; Dizocilpine Maleate - pharmacology; Extracellular Signal-Regulated MAP Kinases - metabolism; Frontal Lobe - drug effects; Frontal Lobe - enzymology; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Rats; Rats, Sprague-Dawley
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145705005882

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.