Effects of midazolam on ERK1,ERK2 and CREB phosphorylation in hippncampal in rats

Abstract

Objective To investigate the effects of midazolam on extracellular signal-regulated kinase 1 (ERK1),ERK2 and cyclic AMP response element binding protein (CREB) phosphorylation in hippocampal in rats.Methods Eighty male SD rats weighing 250-300 g were randomly divided into 2 groups ( n = 40) : group control (group C) and group midazolam (group M).The animals underwent a continuous multi-trial inhibitory avoidance training .The times of trial needed for each animal to attain the learning criterion ( 100 s) were recorded.Each animal was given intraperitoneal midazolam 3 mg/kg or normal saline 2 ml/kg at 15 min before training.The memory retention was tested at 0.5,1,2 and 24 h (n = 8,at each time point)after the training session and the memory latency was recorded.The animals were sacrificed 15 min after administration (T0) and after the memory testing (T1-4) and hippocampns was obtained for determination of phosphorylated ERK1 (p-ERK1),p-ERK2 and p-CREB expression.Results Compared with group C,the times of trial to attain the learning criterion were significantly increased,memory latency shortened at T2-4,ERK1 phosphorylation decreased at T0,3.4 while ERK2 and CREB phosphorylation decreased at T0-4.Conclusion Midazolam can inhibit ERK1,ERK2 and CREB phosphorylation in hippocampal in rats. Key words: Midazolam; Extracellular signal-regulated MAP kinases; DNA-binding protein,cyclic AMP-responsive; Hippocampus