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.
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