title: IL-4 mediated by HSV vector suppresses morphine withdrawal response and decreases TNFα, NR2B, and pC/EBPβ in the periaqueductal gray in rats.
abstract: Chronic opiates induce the development of physical dependence. Opioid physical dependence characterized by withdrawal symptoms, may have very long-lasting effects on the motivation for reward, including the incubation of cue-induced drug-seeking behavior. Elucidation of the mechanisms involved in physical dependence is crucial to developing more effective treatment strategies for opioid dependence. Chronic morphine induces production of proinflammatory cytokines in regional-specific sites of the brain. Interleukin-4 (IL-4) is a prototypical anti-inflammatory cytokine that globally suppresses proinflammatory cytokines. Here, we used recombinant herpes simplex virus vector S4IL4 that encode mouse il4 gene to evaluate the therapeutic potential of IL-4 in naloxone-precipitation morphine withdrawal (MW). One week after microinjection of the vector S4IL4 into the PAG LacZ or mouse IL-4 immunoreactivity in the vlPAG was visualized. ELISA assay showed that vector S4IL4 into the PAG induced the expression of IL-4. S4IL4 blunted the morphine withdrawal syndrome. S4IL4 suppressed the upregulated TNFα, NR2B and pC/EBPβ in the PAG induced by MW. These results show that inhibition of proinflammatory factor in the PAG suppressed MW. This study may provide a novel therapeutic approach to morphine physical withdrawal symptoms.
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: H
authors.initials: H
authors.lastname: Yi
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: T
authors.initials: T
authors.lastname: Iida
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ikegami
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: A
authors.initials: A
authors.lastname: Iida
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Lubarsky
authors.affiliation: Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hao
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000008:administration & dosage; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018139:Simplexvirus / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019966:Substance-Related Disorders / Q000235:genetics / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D009270:Naloxone; D009020:Morphine