Role of spinal neuronal ERK5/CREB signaling pathway in withdrawal responses in morphine-dependent rats
10.3760/cma.j.issn.0254-1416.2014.05.011
- VernacularTitle:脊髓神经元ERK5/CREB信号通路在吗啡依赖大鼠戒断反应中的作用
- Author:
Chunguang WANG
;
Shuqin GUO
;
Xiang TIAN
;
Yanling DING
;
Shuxin YIN
;
Hongwei CHEN
;
Licai ZHANG
- Publication Type:Journal Article
- Keywords:
Extracellular signal-regulated MAP kinases;
cAMP response element binding protein;
Morphine dependence;
Substance withdrawal symptoms;
Spinal cord;
Neurons
- From:
Chinese Journal of Anesthesiology
2014;34(5):563-565
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of spinal neuronal extracellular signal-regulated protein kinases 5/cAMP response element binding protein (ERK5/CREB) signaling pathway in withdrawal responses in morphinedependent rats.Methods Ninety-six adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed,weighing 200-250 g,were randomly divided into 4 groups (n =24 each):normal control group (group A),morphine withdrawal group (group B),dimethyl sulfoxide (DMSO) + morphine withdrawal group (group C) and ERK5 inhibitor BIX02188 + morphine withdrawal group (group D).Morphine dependence (MD) was induced by increasing doses of subcutaneous morphine for 6 days.The initial dose of morphine was 10 mg/kg once a day and was increased by 10 mg/kg once a day from 2nd to 5th days until 50 mg/kg on 6th day in B,C and D groups.Morphine withdrawal response (MW) was induced by intraperitoneal naloxone 4 mg/kg at 4 h after last morphine administration in B,C and D groups.In addition,BIX02188 10 μg and 1％ DMSO 10 μl were injected intrathecally at 1 h before naloxone injection in D and C groups,respectively.MW and morphine withdrawal-induced hyperalgesia were scored.The rats were then sacrificed after hyperalgesia was scored and the spinal cord was removed for determination of CREB and phosphorylated CREB (p-CREB) expression.Results Compared with group A,MW and hyperalgesia scores were significantly increased and the expression of p-CREB was up-regulated in B,C and D groups.Compared with group B,MW and hyperalgesia scores were significantly decreased and the expression of p-CREB was down-regulated in D group,and no significant change was found in group C.Conclusion The spinal neuronal ERK5/CREB signaling pathway is involved in withdrawal responses in morphine-dependent rats.
