Changes in activity of extracellular signal-regulated kinase 5 in distal cerebrospinal fluid contacting neurons in mid-brain of morphine dependent rats

Abstract

Objective To evaluate the changes in the activity of extracellular signal-regulated kinase 5 (ERK5) in the distal cerebrospinal fluid contacting neurons (CSF-CNs) in the mid-brain of morphine dependent rats.Methods Forty-eight male adult Sprague-Dawley rats weighing 230-270 g,were randomly divided into 2 groups (n =24 each) using a random number table:control group (group A) and morphine dependence group (group B).Morphine dependence was induced by increasing doses of subautaneous morphine for 5 consecutive days.The initial dose of morphine was 10 mg/kg twice a day and was increased by 10 mg/kg everyday until 50 mg/kg on 5th dav.The equal volume of normal saline was injected subcutaneously instead of morphine in group A.On 3rd day after morphine dependence was induced,the distal CSF-CNs in the mid-brain was labeled with 30％ cholera toxin subunit B and horseradish peroxidase compound (CB-HRP) 3 μl injected in the lateral cerebral ventricle in the morning.At 4 h after the last injection of morphine,the segments in which CSF-CNs were located were removed,and CB-HRP positive neurons,phosphor-ERK5 (p-ERK5) positive neurons and CB-HRP/p-ERK5 positive neurons were counted.Results Compared with group A,the number of p-ERK5 and CB-HRP/p-ERK5 positive neurons in the mid-brain was significantly increased (P ＜ 0.05),and no significant change was found in CB-HRP positive neurons in group B (P ＞ 0.05).Conclusion The enhanced activity of ERK5 in the distal CSFCNs in the mid-brain may contribute to the development of morphine dependence in rats. Key words: Extracellular signal-regulated MAP kinases; Morphine dependence; Neurons