Opioid addiction is a growing problem for public health, and opioids have correspondingly become more heavily regulated over time. We have previously shown that TRPV1 plays a critical role in morphine addiction using a self-administration paradigm in rats, and the current study evaluates the effects of the TRPV1 signaling pathway on morphine self-administration (SA). We found that treatment with a selective TRPV1 antagonist, SB366791, significantly decreased the morphine SA-induced activation of Ca2⁺/calmodulin-dependent protein kinase II (CaMKII), Akt and the cAMP response element binding protein (CREB) in the nucleus accumbens (NAc). In addition, phospho-PKA and phospho-PKC expression levels were significantly increased in the NAc of the morphine-SA groups, regardless of SB366791 treatment. Finally, local microinjection of SB366791 into the NAc significantly suppressed the maintenance of morphine SA. Taken together, our findings highlight that TRPV1 plays an important role in morphine addiction, likely via activation of the CaMKII-CREB pathway in the NAc.

阿片类药物成瘾是公共卫生中日益严重的问题，随着时间的流逝，阿片类药物也相应地受到越来越严格的管制。先前我们已经证明，在大鼠中使用自我给药范例，TRPV1在吗啡成瘾中起关键作用，并且当前的研究评估了TRPV1信号通路对吗啡自我给药（SA）的影响。我们发现，使用选择性TRPV1拮抗剂SB366791处理可显着降低吗啡SA诱导的Ca2 ⁺激活/钙调蛋白依赖性蛋白激酶II（CaMKII），Akt和伏伏核（NAc）中的cAMP反应元件结合蛋白（CREB）。此外，无论SB366791处理如何，在吗啡-SA组的NAc中磷酸-PKA和磷酸-PKC表达水平均显着增加。最后，将SB366791局部注射到NAc中可显着抑制吗啡SA的维持。两者合计，我们的发现突出表明TRPV1在吗啡成瘾中起重要作用，可能是通过激活NAc中的CaMKII-CREB途径来实现的。