An N-methyl- d-aspartate antagonist, MK-801, preferentially reduces electroconvulsive shock-induced phosphorylation of p38 mitogen-activated protein kinase in the rat hippocampus

• Published in: Neuroscience letters 2000-12, Vol.296 (2), p.101-104
• Main Authors: Ahn, Yong Min, Oh, Seung Wook, Kang, Ung Gu, Park, Joo-Bae, Kim, Yong Sik
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases - drug effects; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Dizocilpine Maleate - pharmacology; Electroconvulsive shock; Electroconvulsive therapy; Electroshock; ERK1/2; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Male; MAP Kinase Kinase 3; MAP Kinase Kinase 6; MAP Kinase Kinase Kinases - drug effects; MAP Kinase Kinase Kinases - metabolism; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Medical sciences; Mitogen-Activated Protein Kinase Kinases - drug effects; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; MK-801; N-methyl- d-aspartate receptor; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; p38; p38 Mitogen-Activated Protein Kinases; Phosphorylation - drug effects; Protein-Tyrosine Kinases - drug effects; Protein-Tyrosine Kinases - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rat hippocampus; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Treatments
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(00)01632-3

Electroconvulsive shock (ECS) activates the mitogen-activated protein kinase (MAPK) family in the rat hippocampus, but the signaling pathways for this activation are not well understood. We investigated whether N-methyl- d-aspartate (NMDA) receptor mediated signaling is involved in the phosphorylation-activation of the MAPK family. The NMDA receptor antagonist, MK-801, dose-dependently reduced ECS-induced phosphorylation of p38 and its upstream kinase MKK6 up to 1 mg/kg. MK-801 also reduced the phosphorylation of ERK1/2 and MEK1, but only at high dosage, 2 mg/kg. Moreover, the reduction in the phosphorylation of p38 and MKK6 was greater than that of ERK1/2 and MEK1. Our results suggest that ECS activates p38 and ERK1/2 partly through an NMDA receptor-mediated signaling system in the rat hippocampus and that NMDA receptor mediated signaling is more responsible for the activation of the MKK6-p38 pathway than the MEK1-ERK pathway.