title: Naloxone-precipitated morphine withdrawal behavior and brain IL-1β expression: comparison of different mouse strains.
abstract: The development of opioid dependence involves classical neuronal opioid receptor activation and is due in part to engagement of glia causing a proinflammatory response. Such opioid-induced glial activation occurs, at least in part, through a non-classical opioid mechanism involving Toll-like-receptor 4 (TLR4). Among the immune factors released following the opioid-glia-TLR4 interaction, interleukin-1β (IL-1β) plays a prominent role. Previous animal behavioral studies have demonstrated significant heterogeneity of chronic morphine-induced tolerance and dependence between different mouse strains. The aim of this study was to investigate whether the heterogeneity of chronic opioid-induced IL-1β expression contributes to differences in opioid tolerance and withdrawal behaviors. Chronic morphine-induced tolerance and dependence were assessed in 3 inbred wild-type mouse strains (Balb/c, CBA, and C57BL/6) and 2 knockout strains (TLR4 and MyD88). Analysis of brain nuclei (medial prefrontal cortex, cortex, brain stem, hippocampus, and midbrain and diencephalon regions combined) revealed that, of inbred wild-type mice, there are significant main effects of morphine treatment on IL-1β expression in the brain regions analyzed (p<0.02 for all regions analyzed). A significant increase in hippocampal IL-1β expression was found in C57BL/6 mice after morphine treatment, whilst, a significant decrease was found in the mPFC region of wild-type Balb/c mice. Furthermore, the results of wild-type inbred strains demonstrated that the elevated hippocampal IL-1β expression is associated with withdrawal jumping behavior. Interestingly, knockout of TLR4, but not MyD88 protected against the development of analgesic tolerance. Gene sequence differences of IL - 1β and TLR4 genes alone did not explain the heterogeneity of dependence behavior between mouse strains. Together, these data further support the involvement of opioid-induced CNS immune signaling in dependence development. Moreover, this study demonstrated the advantages of utilizing multiple mouse strains and indicates that appropriate choice of mouse strains could enhance future research outcomes.
authors: Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia.
authors: Liang
authors: L
authors: Liu
authors: Janet K
authors: JK
authors: Coller
authors: Linda R
authors: LR
authors: Watkins
authors: Andrew A
authors: AA
authors: Somogyi
authors: Mark R
authors: MR
authors: Hutchinson
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004361:Drug Tolerance; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000378:metabolism*; D008810:Mice, Inbred C57BL / Q000378:metabolism*; D008808:Mice, Inbred CBA / Q000378:metabolism*; D018345:Mice, Knockout; D009021:Morphine Dependence / Q000276:immunology / Q000503:physiopathology*; D009043:Motor Activity / Q000187:drug effects; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology* / Q000633:toxicity; D009292:Narcotic Antagonists / Q000494:pharmacology* / Q000633:toxicity; D009457:Neuroglia / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009292:Narcotic Antagonists; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009270:Naloxone