PMID- 21447380 OWN - NLM STAT- MEDLINE DCOM- 20111207 LR - 20220408 IS - 1090-2139 (Electronic) IS - 0889-1591 (Print) IS - 0889-1591 (Linking) VI - 25 IP - 6 DP - 2011 Aug TI - Naloxone-precipitated morphine withdrawal behavior and brain IL-1beta expression: comparison of different mouse strains. PG - 1223-32 LID - 10.1016/j.bbi.2011.03.016 [doi] AB - 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-1beta (IL-1beta) 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-1beta 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-1beta expression in the brain regions analyzed (p<0.02 for all regions analyzed). A significant increase in hippocampal IL-1beta 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-1beta 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 - 1beta 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Liu, Liang AU - Liu L AD - Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia. FAU - Coller, Janet K AU - Coller JK FAU - Watkins, Linda R AU - Watkins LR FAU - Somogyi, Andrew A AU - Somogyi AA FAU - Hutchinson, Mark R AU - Hutchinson MR LA - eng GR - DA024044/DA/NIDA NIH HHS/United States GR - R01 DA017670-04/DA/NIDA NIH HHS/United States GR - DA015642/DA/NIDA NIH HHS/United States GR - K02 DA015642/DA/NIDA NIH HHS/United States GR - DA017670/DA/NIDA NIH HHS/United States GR - K05 DA024044/DA/NIDA NIH HHS/United States GR - R01 DA017670/DA/NIDA NIH HHS/United States GR - K02 DA015642-04/DA/NIDA NIH HHS/United States GR - R01 DE017782-04/DE/NIDCR NIH HHS/United States GR - R01 DA023132/DA/NIDA NIH HHS/United States GR - K05 DA024044-04/DA/NIDA NIH HHS/United States GR - R01 DE017782/DE/NIDCR NIH HHS/United States GR - DE017782/DE/NIDCR NIH HHS/United States GR - R01 DE021966/DE/NIDCR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110403 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 0 (Interleukin-1beta) RN - 0 (Lipopolysaccharides) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Narcotic Antagonists) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 36B82AMQ7N (Naloxone) SB - IM MH - Animals MH - Brain/*metabolism MH - Cells, Cultured/drug effects/metabolism MH - Drug Tolerance MH - Hippocampus/metabolism/physiopathology MH - Inflammation MH - Interleukin-1beta/*biosynthesis/genetics/physiology MH - Leukocytes/drug effects/metabolism MH - Lipopolysaccharides/pharmacology MH - Male MH - Mice MH - Mice, Inbred BALB C/*metabolism MH - Mice, Inbred C57BL/*metabolism MH - Mice, Inbred CBA/*metabolism MH - Mice, Knockout MH - Morphine Dependence/immunology/*physiopathology MH - Motor Activity/drug effects MH - Myeloid Differentiation Factor 88/deficiency/genetics/physiology MH - Naloxone/*pharmacology/toxicity MH - Narcotic Antagonists/*pharmacology/toxicity MH - Neuroglia/physiology MH - Neuroimmunomodulation/physiology MH - Polymorphism, Single Nucleotide MH - Sequence Analysis, DNA MH - Substance Withdrawal Syndrome/*etiology/metabolism MH - Toll-Like Receptor 4/deficiency/genetics/physiology PMC - PMC3142610 MID - NIHMS285683 COIS- Conflicts of interest All authors declare no conflicts of interest. EDAT- 2011/03/31 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/08/01 CRDT- 2011/03/31 06:00 PHST- 2010/12/14 00:00 [received] PHST- 2011/03/16 00:00 [revised] PHST- 2011/03/23 00:00 [accepted] PHST- 2011/03/31 06:00 [entrez] PHST- 2011/03/31 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/08/01 00:00 [pmc-release] AID - S0889-1591(11)00084-5 [pii] AID - 10.1016/j.bbi.2011.03.016 [doi] PST - ppublish SO - Brain Behav Immun. 2011 Aug;25(6):1223-32. doi: 10.1016/j.bbi.2011.03.016. Epub 2011 Apr 3.