NO mediated increase of Fos protein and NMDA(1A) R mRNA expression in rat spinal cord during morphine withdrawal

AIM: To investigate the effects of nitric oxide (NO) on activation of the r at spinal cord neurons during naloxone-precipitated morphine withdrawal. ME THODS: Fos immunocytochemistry, NADPH-d histochemistry, Fos/ NADPH-d double -labeling, intrathecal injection, antisense oligonucleotides (AS-ONs) techn iques, and RT-PCR were used. RESULTS: Acute administration of naloxone and chronic administration of morphine did not change the expression of Fos pro tein and NADPH-d positive neurons, and there was no expression of Fos/ NADP H-d double-labeled neurons in the spinal cord of rats. Morphine withdrawal increased the expression of Fos protein, NADPH-d positive, ad Fos/NADPH-d d ouble-labeled neurons, and they were observed in all the laminae of the mt Spinal cord. Intrathecal injection of nNOS antisense oligonucleotides (nNOS -AS) inhibited the increase of Fos protein and NMDA(1A)R mRNA expression in the rat spinal cord during morphine withdrawal and decreased the scores of morphine withdrawal symptoms. The effect of nNOS-AS was greater than that of eNOS-AS. There was no effect in nNOS sense oligonucleotides (nNOS-S) gro up. CONCLUSION: NO mediated the increase of Fos protein and NMDA1AR mRNA ex pression in the mt spinal cord during morphine withdrawal.