NO mediated increase of Fos protein and NMDA1A R mRNA expression in rat spinal cord during morphine withdrawal.
OBJECTIVE
To investigate the effects of nitric oxide (NO) on activation of the rat spinal cord neurons during naloxone-precipitated morphine withdrawal.


METHODS
Fos immunocytochemistry, NADPH-d histochemistry, Fos/NADPH-d double-labeling, intrathecal injection, antisense oligonucleotides (AS-ONs) techniques, and RT-PCR were used.


RESULTS
Acute administration of naloxone and chronic administration of morphine did not change the expression of Fos protein and NADPH-d positive neurons, and there was no expression of Fos/NADPH-d double-labeled neurons in the spinal cord of rats. Morphine withdrawal increased the expression of Fos protein, NADPH-d positive, and Fos/NADPH-d double-labeled neurons, and they were observed in all the laminae of the rat 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) group.


CONCLUSIONS
NO mediated the increase of Fos protein and NMDA1A R mRNA expression in the rat spinal cord during morphine withdrawal.
Gao
J L
JL
Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Zeng
Y M
YM
Zhang
L C
LC
Gu
J
J
Liu
H F
HF
Zhou
W H
WH
Yang
G D
GD
D000818:Animals; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D009020:Morphine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C496322:Nos1 protein, rat