title: [The role of the spinal cord inducible nitric oxide synthase in morphine dependence and naloxone-precipitated withdrawal rats].
abstract: OBJECTIVE
  To explore if induced nitric oxide in the spinal cord mediates withdrawal syndrome in morphine-dependent rats.
  
  
  METHODS
  Male SD rats weighing 200-250 g were employed in the present study. 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 each 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). Inducible nitric oxide synthase (iNOS) inhibitors aminoguanidine (AG) was intrathecally injected 30 min before the administration of naloxone. All the rats were divided into four groups: control group, dependence group, withdrawal group, AG group. Morphine withdrawal score, touch evoked agitation scores (TEA scores), immunohistochemical and Western blot technique were used to evaluate morphine withdrawal response and the expression of iNOS in the spinal cord.
  
  
  RESULTS
  Intrathecal injection of iNOS inhibitors AG could alleviate morphine withdrawal symptoms. Morphine withdrawal scores and touch evoked agitation scores in AG group were significantly lower than that of withdrawal group (P < 0.05). iNOS positive neurons in dorsal horn of AG group were significantly lower than that of withdrawal group (P < 0.05). Level of iNOS protein in spinal cord of AG group was significantly lower than that of withdrawal group (P < 0.05).
  
  
  CONCLUSIONS
  Induced nitric oxide in the spinal cord may mediate withdrawal syndrome in morphine-dependent rats.
authors.affiliation: Department of Anesthesiology, 1st Hospital of Huai'an, Affiliated Hospital of Nanjing Medical University, Huai'an 223300, China. liuhailin_1971@163.com
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Liu
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Qian
authors.forename: Xiang-Cheng
authors.initials: XC
authors.lastname: Li
mesh_terms: D000818:Animals; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D009270:Naloxone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat