Ahn Yong Min, Seo Myoung Suk, Kim Se Hyun, Kim Yeni, Juhnn Yong-Sung, Kim Yong Sik
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.
Int J Neuropsychopharmacol. 2006 Aug;9(4):451-6. doi: 10.1017/S1461145705005882. Epub 2005 Aug 4.
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.
MK-801可在动物中诱发拟精神病行为变化。细胞外信号调节激酶（ERKs）在精神分裂症的发病机制以及抗精神病药物和拟精神病药物的作用中发挥重要作用。我们观察了MK-801给药后大鼠额叶皮质中ERK信号通路相关分子的磷酸化及其与大鼠行为的关联。注射0.25 - 1mg/kg的MK-801后，与溶剂处理相比，ERK磷酸化水平降低，且大鼠的活动增加。在2mg/kg处理后，ERK磷酸化增加，大鼠的运动能力开始下降。用4 - 8mg/kg处理后，ERK磷酸化再次降低，大鼠表现出运动减少和共济失调。在1或2mg/kg处理后，ERK磷酸化水平在15分钟至90分钟内保持稳定。Ser338 - c - Raf和MEK的磷酸化表现出与ERK相似的剂量依赖性和时间模式。综上所述，MK-801在大鼠额叶皮质中引起的Ser338 - c - Raf - MEK - ERK磷酸化呈现出特定模式，并且可能与MK-801诱导的行为变化相关。
