[MEK inhibitors suppressed expression of NOS in spinal cord of morphine-induced dependent and withdrawal rats].

OBJECTIVE

To explore the effects of intrathecal injection of mitogen-activated protein kinases inhibitors U0126 on the behavioral changes of morphine-induced dependent and withdrawal rats and the expression of nitric oxide synthase (NOS) in spinal cord.

METHODS

All the rats were divided into 4 groups: control group, dependent group, withdrawal group, U0126 group (5 microg). Global withdrawal score, Touch evoked agitation scores (TEA score), immunohistochemical and Western blot technique were undertaken to evaluate behavioral changes and expression of FOS, nNOS and iNOS in spinal cord respectively.

RESULTS

The results showed that intrathecal administration of U0126 significantly alleviated withdrawal symptom, withdrawal scores of U0126 group (22.5 +/- 4.09) were significantly lower than than those of withdrawal group (28.6 +/- 4.89) (P < 0.05). TEA scores of withdrawal group were 13.5 +/- 2.55, which were significantly higher than those of U0126 group (10.0 +/- 2.76, P < 0.05). Fos-like positive neurons in dorsal horn of withdrawal group were 380 +/- 71, which were higher than those of U0126 group(287 +/- 54, P < 0.05). Also nNOS and iNOS positive neurons in dorsal horn of U0126 group were 180 +/- 32, 10.8 +/- 2.8 respectively, which were significantly lower than that of withdrawal group (239 +/- 45, 16.8 +/- 5.1, P < 0.05). Compared with withdrawal group, levels of nNOS and iNOS protein in spinal cord of U0126 group were significantly lower.

CONCLUSION

MEK inhibitors could alleviate withdrawal symptom of morphine-induced dependent rats and could suppress expression of NOS in spinal cord, and extracellular signal-regulate kinase (ERK) might involve the expression of NOS in spinal cord.