title: Suppression of acute morphine withdrawal syndrome by adenovirus-mediated β-endorphin in rats.
abstract: BACKGROUND
  Endogenous β-endorphin (β-EP) in the central nervous system (CNS) is decreased upon opioid addiction. The current study examined whether exogenous β-EP, delivered using an adenoviral vector into the CNS could attenuate morphine withdrawal syndrome in rats.
  
  
  METHODS
  The model of opioid-dependent rats was set up by receiving subcutaneous injection of morphine using an escalating regimen for 6days (5, 10, 20, 40, 50, 60mg/kg, three times/day). The adenovirus mediated β-EP gene was constructed based on our previous work. The ilea of opioid-dependent rats were isolated and treated with the supernatant of Ad-NEP. The basic and naloxone-induced (4μm/l) contractions of dependent ilea were recorded. The Ad-NEP was injected into the left lateral ventricle of the addition rats. The expression of the β-EP gene was verified by radioimmunoassay of the cerebrospinal fluid (CSF) and immunocytochemistry for β-EP. Withdrawal syndrome was evaluated after intraperitoneal injection of naloxone.
  
  
  RESULTS
  The contractions of dependent ilea were attenuated with supernatant containing β-EP expressed by Ad-NEP. Injection of the Ad-NEP resulted in significant increases in β-EP level in the CSF and β-EP-positive neurons. Rats receiving adenovirus carrying the β-EP gene had significantly less severe withdrawal symptoms upon naloxone challenge.
  
  
  CONCLUSIONS
  Exogenous β-EP mediated by adenovirus could attenuate withdrawal syndrome in morphine-dependent rats.
authors: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, 200438, People's Republic of China.
authors: Yan
authors: Y
authors: He
authors: Fei-Xiang
authors: FX
authors: Wu
authors: Xue-Rong
authors: XR
authors: Miao
authors: Xue-Wu
authors: XW
authors: Xu
authors: Yu-Ming
authors: YM
authors: Sun
authors: Cai-Yang
authors: CY
authors: Chen
authors: Wei-Feng
authors: WF
authors: Yu
mesh_terms: D000208:Acute Disease; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D001615:beta-Endorphin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology*
chemical_list: D001615:beta-Endorphin; D009020:Morphine