Calcitonin receptor signal: a potential target for opioid use disorder?
Calcitonin receptor signal: a potential target for opioid use disorder?
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降钙素受体信号：阿片类药物使用障碍的潜在目标？
DOI：
10.1038/s41386-023-01702-4
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Venniro,Marco
中科院分区：
文献类型：
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作者：
Marino,RosaAM;Venniro,Marco
如果我们问任何成瘾神经科学研究人员他们的主要科学目标和梦想，压倒性的反应无疑是发现可以预防和破坏药物成瘾各个阶段的治疗方法和目标。纵观我们领域的历史，这一直是我们社区的共同目标，跨越了几十年[1]。尽管有崇高的意图，热切的努力和重大的投资，但严峻的现实仍然是，治疗方案在很大程度上保持不变[2]。这种技术状态的停滞越来越引起失望，并对我们领域的有效性提出了怀疑。虽然这一背景听起来可能愤世嫉俗和悲观，但重要的是要注意，这不是结束。作为成瘾神经科学领域的科学家，我们承认我们过去的错误和失败。尽管如此，我们仍坚持寻求创造和提出新的解决办法和办法。我们致力于从以往的失误中吸取教训，并致力于不断探索创新途径[3]。近年来，人们对探索治疗药物成瘾的潜在药物疗法越来越感兴趣。在各种方法中，一个重要的焦点领域是靶向肠-脑轴内的神经肽及其受体[4]。降钙素受体（CTR）已成为这方面特别有前途的例子。CTR的药理学活化已经显示出减少药物诱导的中脑边缘多巴胺系统活化和药物服用的前景。然而，CTR在阿片类药物成瘾中的作用仍然是一个关键的研究领域。这是因为目前阿片类药物成瘾的治疗主要依赖于使用全部或部分μ阿片受体激动剂和拮抗剂，这被认为是有效的治疗方法。然而，鉴于目前阿片类药物的流行和对更有效治疗的迫切需求，研究CTR和其他信号通路的参与可能为开发更有针对性和可能更有效的阿片类药物成瘾治疗提供新的途径。在这一期的《神经精神药理学》中，张等。[5]深入研究这一主题，以进一步扩大我们对CTR参与阿片类药物自我给药的理解，特别强调核内（NAc）壳，因为它在介导阿片类药物相关行为中起着关键作用。在这篇综合性论文中，作者最初开始了一项令人印象深刻的奋进，以表征NAc中CTRs表达的细胞类型特异性模式。他们使用了大量的国家-
If we were to ask any addiction neuroscience researcher about their main scientific goal and dream, the overwhelming response would undoubtedly be to discover treatments and targets that can prevent and disrupt the various phases of drug addiction. Throughout the history of our field, this has been the shared objective for our community, spanning several decades [1]. Despite the noble intentions, fervent efforts, and significant investments, the stark reality remains that treatment options have remained largely unchanged [2]. This stagnation in the state of the art has increasingly caused disappointment and raised doubts about the validity of our field. While this background may sound cynical and pessimistic, it is important to note that this is not the end. As scientists in the addiction neuroscience field, we acknowledge our past mistakes and failures. Nevertheless, we persist in our pursuit of creating and proposing new solutions and approaches. We are committed to learning from our previous missteps and are dedicated to the ongoing exploration of innovative avenues [3].In recent years, there has been a growing interest in exploring potential pharmacotherapies to treat drug addiction. Among various approaches, one significant area of focus has been targeting neuropeptides and their receptors within the gut-brain axis [4]. Calcitonin receptors (CTRs) have emerged as a particularly promising example in this regard. Pharmacological activation of CTRs has shown promise in reducing drug-induced activation of the mesolimbic dopamine system and drug taking. However, the role of CTRs in opioid addiction remains a critical area for investigation. This is because current therapies for opioid addiction predominantly rely on the use of full or partial mu opioid receptor agonists and antagonists, which are considered effective treatments. However, given the current opioid epidemic and the urgent need for more effective treatments, investigating the involvement of CTRs and other signaling pathways could provide new avenues for developing more targeted and potentially more effective treatments for opioid addiction. In this issue of Neuropsychopharmacology, Zhang et al.[5] delve into this topic to further expand our understanding of the involvement of CTRs in opioid self-administration with a specific emphasis on the nucleus accumbens (NAc) shell because of its pivotal role in mediating opioid-related behaviors. In this comprehensive paper, the authors initially embarked on an impressive endeavor to characterize cell type-specific patterns of CTRs expression in the NAc. They employed a wide array of state-of-