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Different roles of the spinal protein kinase C #alpha# and #gamma# in morphine dependence and naloxone--precipitated withdrawal

Cao Junli, Ding Hailei, He Jianhua, Zhang Licai, Wang Junke, Zeng Yinming

Department of Anesthesiology, Affiliated Hospital of First Clinical College, China Medical University.Shenyang 110001,Liaoning；China

Abstract

Our previous studies showed that spinal neurons sensitization was involved in morphine withdrawal response. This study was to investigate the roles of spinal protein kinase C (PKC) #alpha#，#gamma# in morphine dependence and naloxone-precipitated withdrawal response. To set up morphine dependence model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg in the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, ip). Chelerythrine chloride (CHE), a PKC inhibitor, was intrathecally injected 30 min before the administration of naloxone. The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed. One hour after naloxone-precipitated withdrawal, Fos protein expression was assessed by immunohistochemical analysis and western blot was used to detect the expression of cytosol and membrane fraction of PKC #alpha# and #gamma# in the rat spinal cord. The results showed that intrathecal administration of CHE decreased the scores of morphine withdrawal, attenuated morphine withdrawal-induced allodynia and also inhibited the increase of Fos protein expression in the spinal cord of morphine withdrawal rats. The expression of cytosol and membrane fraction of PKC #alpha# was significantly increased in the spinal cord of rats with morphine dependence. Naloxone-precipitated withdrawal induced PKC #alpha# translocation from cytosol to membrane fraction, which was prevented by intrathecal administration of CHE. During morphine dependence, not naloxone-precipitated withdrawal, PKC #gamma# in the spinal cord translocated from cytosol to membrane fraction, and intrathecal administration of CHE did not change the expression of PKC #gamma# in the spinal cord of naloxone-precipitated withdrawal rats. It is suggested that up-regulation and translocation of PKC in the spinal cord contribute to morphine dependence and naloxone-precipitated withdrawal in rats and that PKC #alpha# and #gamma# play different roles in the above-mentioned effect.

Key words: morphine dependence;substance withdrawal syndrome;Spinal cord;Protein kinase C;translocation;allodynia

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Citing This Article：

Cao Junli, Ding Hailei, He Jianhua, Zhang Licai, Wang Junke, Zeng Yinming. Different roles of the spinal protein kinase C #alpha# and #gamma# in morphine dependence and naloxone--precipitated withdrawal. Acta Physiol Sin 2005; 57 (2): (in Chinese with English abstract).