The different roles of the spinal protein nNOS and iNOS in morphine naloxone-precipitated withdrawal response / 中国应用生理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of intrathecal injection of neuronal nitric oxide synthase (nNOS) inhibitors 7-Nitroindazole (7-Ni) and inducible nitric oxide synthase(iNOS) inhibitors aminoguanidine (AG) on the behavioral changes of morphine-induced dependent and withdrawal rats; the expression of Fos, nNOS and iNOS in spinal cord.</p><p><b>METHODS</b>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 every 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). 7-Ni, an nNOS inhibitor or iNOS inhibitors AG were intrathecally injected 30 min before the administration of naloxone respectively. 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 nNOS and iNOS in the rat spinal cord.</p><p><b>RESULTS</b>Intrathecal administration of nNOS inhibitor 7-Ni and iNOS inhibitors AG 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. nNOS and iNOS positive neurons in dorsal horn in nNOS group and iNOS group were significantly lower than that in withdrawal group. Compared with withdrawal group, level of nNOS and iNOS protein in spinal cord in nNOS group and iNOS group were significantly lower.</p><p><b>CONCLUSION</b>It is suggested that nNOS and iNOS in the spinal cord may contribute to naloxone-precipitated withdrawal in rats and may play different roles in the above-mentioned effect.</p>