Interleukin-1 receptor-associated kinase 4 (IRAK4) in the nucleus accumbens regulates opioid-seeking behavior in male rats.
Interleukin-1 receptor-associated kinase 4 (IRAK4) in the nucleus accumbens regulates opioid-seeking behavior in male rats.
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DOI：
10.1016/j.bbi.2021.12.014
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Li JX
中科院分区：
文献类型：
--
作者：
Wu R;Liu J;Vu J;Huang Y;Dietz DM;Li JX
阿片类药物成瘾仍然是一个严重的健康问题。虽然以神经元为中心的研究已经对阿片类药物成瘾产生了重要的见解，但非神经元机制对阿片类药物相关行为适应的贡献已开始得到认识。 Toll 样受体 4 (TLR4) 是一种模式识别受体，已被广泛认为与阿片类药物相关行为有关。 Interleukin-1 受体相关激酶 4 (IRAK4) 是 TLR4 反应所必需的激酶，然而，IRAK4 在阿片类药物相关反应中的潜在作用尚未得到研究。在这里，我们探讨了 IRAK4 在雄性大鼠提示诱导的阿片类药物寻求行为中的作用。我们发现，自我给予吗啡会增加大鼠伏隔核 (NAc) 中 IRAK4 的磷酸化水平；在吗啡消退和提示诱导恢复测试后，IRAK4 信号仍保持激活状态。 NAc 核心中 IRAK4 的全身和局部抑制均减弱了线索诱导的吗啡寻求行为，而不影响运动活性和线索诱导的蔗糖寻求行为。此外，抑制IRAK4也减少了线索诱导的芬太尼寻求的恢复。我们的研究结果表明，IRAK4 在阿片类药物复发样行为中发挥着重要作用，并为先天免疫与药物成瘾之间的关联提供了新的证据。
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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影响因子：
3.6
作者：
Greenwell, Thomas N.;Walker, Brendan M.;Cottone, Pietro;Zorrilla, Eric P.;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
2.9
作者：
Doyle HH;Murphy AZ
通讯作者：
Murphy AZ
影响因子：
15.1
作者：
Hutchinson, Mark R.;Zhang, Yingning;Shridhar, Mitesh;Evans, John H.;Buchanan, Madison M.;Zhao, Tina X.;Slivka, Peter F.;Coats, Benjamen D.;Rezvani, Niloofar;Wieseler, Julie;Hughes, Travis S.;Landgraf, Kyle E.;Chan, Stefanie;Fong, Stephanie;Phipps, Simon;Falke, Joseph J.;Leinwand, Leslie A.;Maier, Steven F.;Yin, Hang;Rice, Kenner C.;Watkins, Linda R.
通讯作者：
Watkins, Linda R.
DOI：
10.1523/jneurosci.1729-12.2012
发表时间：
2012-10-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cameron B;Tse W;Lamb R;Li X;Lamb BT;Landreth GE
通讯作者：
Landreth GE
影响因子：
15.1
作者：
Ezeomah, Chiomah;Cunningham, Kathryn A.;Cisneros, Irma E.
通讯作者：
Cisneros, Irma E.