title: M2 muscarinic receptor of spinal cord mediated increase of nNOS expression in locus coeruleus during morphine withdrawal.
abstract: 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.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China. xmcfa@public.xz.js.cn
authors.forename: Wei-Bin
authors.initials: WB
authors.lastname: Chou
authors.forename: Yin-Ming
authors.initials: YM
authors.lastname: Zeng
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Duan
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Yang
mesh_terms: 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*
chemical_list: 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