期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 101, 期 -, 页码 37-48出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2021.12.014
关键词
IRAK4; Opioid addiction; Neuroimmune response; Cue-induced opioid-seeking; Nucleus accumbens; Relapse
资金
- National Institutes of Health National Institute on Drug Abuse [R21DA040777, R01DA047967]
The study reveals the important role of immune molecule IRAK4 in opioid-related behaviors, and inhibition of IRAK4 can reduce opioid-seeking behavior.
Opioid addiction remains a severe health problem. While substantial insights underlying opioid addiction have been yielded from neuron-centric studies, the contribution of non-neuronal mechanisms to opioid-related behavioral adaptations has begun to be recognized. Toll-like receptor 4 (TLR4), a pattern recognition receptor, has been widely suggested in opioid-related behaviors. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a kinase essential for TLR4 responses, However, the potential role of IRAK4 in opioid-related responses has not been examined. Here, we explored the role of IRAK4 in cue-induced opioid-seeking behavior in male rats. We found that morphine self-administration increased the phosphorylation level of IRAK4 in the nucleus accumbens (NAc) in rats; the IRAK4 signaling remained activated after morphine extinction and cue-induced reinstatement test. Both systemic and local inhibition of IRAK4 in the NAc core attenuated cue-induced morphine-seeking behavior without affecting the locomotor activity and cue-induced sucrose-seeking. In addition, inhibition of IRAK4 also reduced the cue-induced reinstatement of fentanyl-seeking. Our findings suggest an important role of IRAK4 in opioid relapse-like behaviors and provide novel evidence in the association between innate immunity and drug addiction.
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