M2 muscarinic receptor of spinal cord mediated increase of nNOS expression in locus coeruleus during morphine withdrawal.
OBJECTIVE
To investigate the effects of different muscarinic receptor (M) subtypes in the spinal cord on the scores of naloxone-precipitated morphine-withdrawal symptoms and the changes of nNOS expression in locus coeruleus (LC).


METHODS
nNOS immunohistochemistry, intrathecal injection (it), and antisense oligonucleotides (AS-ONs) techniques were used.


RESULTS
Intrathecal injection of M2-antisense oligonucleotides (M2-AS) decreased the scores of morphine withdrawal symptoms. M1-AS attenuated morphine-withdrawal symptoms, but the effect was less than that of M2-AS. The expression of nNOS positive neurons in the LC increased in morphine-dependent rats and increased to a greater extent during morphine withdrawal. Intrathecal injection of M2-AS inhibited the increase of nNOS expression in LC during morphine-withdrawal, but there was no effect in case of M1-AS.


CONCLUSIONS
M2 muscarinic receptor of spinal cord mediated the increase of nNOS expression in LC during morphine withdrawal.
Chou
Wei-Bin
WB
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China. xmcfa@public.xz.js.cn
Zeng
Yin-Ming
YM
Duan
Shi-Ming
SM
Zhou
Wen-Hua
WH
Gu
Jun
J
Yang
Guo-Dong
GD
D000818:Animals; D008125:Locus Coeruleus / Q000201:enzymology*; D008297:Male; D009021:Morphine Dependence; D009270:Naloxone / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D016376:Oligonucleotides, Antisense; D051381:Rats; D017207:Rats, Sprague-Dawley; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000201:enzymology*
D016376:Oligonucleotides, Antisense; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D009270:Naloxone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat