Essential role of toll-like receptor 2 in morphine-induced microglia activation in mice.
Opioids are powerful pain relievers, but also potent inducers of dependence and tolerance. Chronic morphine administration (via subcutaneous pellet) induces morphine dependence in the nucleus accumbens, an important dependence region in the brain, yet the cellular mechanisms are mostly unknown. Toll-like receptor 2 (TLR2) plays an essential function in controlling innate and inflammatory responses. Using a knockout mouse lacking TLR2, we assessed the contribution of TLR2 to microglia activation and development of morphine dependence. We report here that mice deficient in TLR2 inhibit morphine-induced the levels of microglia activation and proinflammatory cytokines. Moreover, in TLR2 knockout mice the main symptoms of morphine withdrawal were significantly attenuated. Our data reveal that TLR2 plays a critical role in morphine-induced microglia activation and dependence.
Department of Internal Medicine, College of Medicine, East Tennessee State University, Johnson City, TN 37614, United States.
Yi
Y
Zhang
Hui
H
Li
Yi
Y
Li
Xiuli
X
Sun
Mengyang
M
Zhu
Gregory
G
Hanley
Gene
G
Lesage
Deling
D
Yin
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D016207:Cytokines; D009294:Narcotics; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D009020:Morphine