title: Interferon-alpha reinstates morphine-conditioned place preference through opioid receptors in rats.
abstract: Cytokine interferon-alpha (IFN-alpha) is an immunomodulator and neuromodulator, which modulates central nervous system function partially by activating opioid receptors. However, the role that IFN-alpha plays in relapse to drug abuse is still largely unknown. Thus, we studied whether human recombinant INF-alpha (rIFN-alpha) would reinstate morphine-conditioned place preference (CPP) in rats. In Experiment 1, rats were trained for morphine-CPP with 8-day alternate subcutaneous (s.c.) injections of morphine and saline, and the effect of human rIFN-alpha (20 000 IU/5 microl, intracerebroventricularly) on CPP reinstatement was examined after extinction. In Experiment 2, rats underwent morphine (5 mg/kg, s.c.) unconditioned training with 8 daily alternate injections of morphine (5 mg/kg, s.c.) and saline. Then, the effect of human rIFN-alpha (20 000 IU/5 microl, intracerebroventricularly) on reinstatement of CPP was examined after extinction. In Experiment 3, the effect of opioid receptor antagonist naloxone (1 mg/kg, intraperitoneally) on human rIFN-alpha-induced reinstatement of morphine-CPP was investigated. We found that human rIFN-alpha reinstated morphine-CPP in rats trained under morphine conditioning after extinction, but did not affect CPP in rats that underwent unconditioned training. Naloxone significantly inhibited human rIFN-alpha-induced reinstatement of morphine-CPP. These results indicate that IFN-alpha is a stimulus for reinstatement of morphine-CPP by activation of opioid receptors, which extends our understanding on the high comorbidity of heroin relapse and viral infection.
authors.affiliation: aAffiliated Hospital and School of Pharmacology of Guiyang Medical College, Guiyang, China bNational Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Jun-Yuan
authors.initials: JY
authors.lastname: Lang
authors.forename: Ji-Shi
authors.initials: JS
authors.lastname: Wang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhai
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Lu