Interleukin-1 receptor-associated kinase 4 (IRAK4) in the nucleus accumbens regulates opioid-seeking behavior in male rats.
Brain Behav Immun
; 101: 37-48, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-34958862
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quinasas Asociadas a Receptores de Interleucina-1
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Comportamiento de Búsqueda de Drogas
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Trastornos Relacionados con Opioides
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Núcleo Accumbens
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article