Roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinase 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats

Abstract

Objective To investigate the roles of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 signaling pathway in naloxone-induced withdrawal response in morphine-dependent rats. Methods Ninety-six adult male SD rats weighting 230-250 g were randomly divided into 4 groups: control group, withdrawal group, DMSO group and MK801 group. Rats were subcutaneously injected with morphine. On day 6, rats were injected with naloxone (intraperitoneal) to precipitate morphine withdrawal syndromes. To identify the function of NMDAR-ERK5 signaling pathway in morphine withdrawal, morphine withdrawal-like behavior test and western blot technique were used in this research. The scores of morphine withdrawal symptom, morphine withdrawal-induced allodynia and the activation of ERK5 in spinal cord were observed after intrathecal injection of MK801. Results There was no withdrawal symptoms and withdrawal-induced allodynia in group A after intraperitoneal injection of naloxone. Compared with group A, withdrawal score (45.2±7.3), score of withdrawal-induced allodynia (14.4±3.7) of group B, withdrawal score (44.7±6.2), score of withdrawal-induced allodynia (13.2±2.7) of group C and withdrawal score (28.3±1.6), score of withdrawal-induced allodynia (5.9±1.1) of group D were significantly increased (P<0.05). Compared with group C, the total withdrawal score (28.3±1.6), score of withdrawal-induced allodynia (5.9±1.1) of group D were significantly decreased (P<0.05). Compared with group A, the expression of spinal p-ERK5 of group B (12 848±621) and group C (12 579±396) were significantly increased (P<0.05). Compared with group C, the expression of spinal p-ERK5 of group D (5 123±546) was significantly decreased (P<0.05). Conclusion The signaling pathway of spinal N-methyl-D-aspartic acid receptor-extracellular signal-regulated protein kinases 5 contributes to naloxone-induced withdrawal response in morphine-dependent rats. Key words: Morphine dependence; Withdrawal symptoms; Spinal cord; N-methyl-D-aspartic acid receptor; Extracellular signal-regulated kinase 5