Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Service Hospitalier Frédéric Joliot, 4 place du général Leclerc, 91401, Orsay, France.
Eur J Nucl Med Mol Imaging. 2021 Dec;49(1):186-200. doi: 10.1007/s00259-021-05408-x. Epub 2021 May 27.
Recent research in last years in substance use disorders (SUD) synthesized a proinflammatory hypothesis of SUD based on reported pieces of evidence of non-neuronal central immune signalling pathways modulated by drug of abuse and that contribute to their pharmacodynamic actions. Positron emission tomography has been shown to be a precious imaging technique to study in vivo neurochemical processes involved in SUD and to highlight the central immune signalling actions of drugs of abuse.
In this review, we investigate the contribution of the central immune system, with a particular focus on translocator protein 18 kDa (TSPO) imaging, associated with a series of drugs involved in substance use disorders (SUD) specifically alcohol, opioids, tobacco, methamphetamine, cocaine, and cannabis.
The large majority of preclinical and clinical studies presented in this review converges towards SUD modulation of the neuroimmune responses and TSPO expression and speculated a pivotal positioning in the pathogenesis of SUD. However, some contradictions concerning the same drug or between preclinical and clinical studies make it difficult to draw a clear picture about the significance of glial state in SUD.
Significant disparities in clinical and biological characteristics are present between investigated populations among studies. Heterogeneity in genetic factors and other clinical co-morbidities, difficult to be reproduced in animal models, may affect findings. On the other hand, technical aspects including study designs, radioligand limitations, or PET imaging quantification methods could impact the study results and should be considered to explain discrepancies in outcomes.
The supposed neuroimmune component of SUD provides new therapeutic approaches in the prediction and treatment of SUD pointing to the central immune signalling.
近年来,物质使用障碍(SUD)领域的最新研究基于药物滥用调节的非神经元中枢免疫信号通路的报告证据,综合提出了 SUD 的促炎假说,这些证据有助于解释其药效作用。正电子发射断层扫描(PET)已被证明是一种宝贵的成像技术,可用于研究 SUD 中涉及的体内神经化学过程,并突出药物滥用的中枢免疫信号作用。
在本综述中,我们研究了中枢免疫系统的贡献,特别是关注与一系列物质使用障碍(SUD)相关的药物(如酒精、阿片类药物、烟草、安非他命、可卡因和大麻)的 18 kDa 转位蛋白(TSPO)成像。
本综述中呈现的绝大多数临床前和临床研究都集中在 SUD 对神经免疫反应和 TSPO 表达的调节上,并推测其在 SUD 的发病机制中具有关键作用。然而,一些关于同一药物或临床前和临床研究之间的矛盾,使得很难清楚地了解胶质状态在 SUD 中的意义。
研究之间的调查人群在临床和生物学特征方面存在显著差异。遗传因素和其他临床合并症的异质性,难以在动物模型中重现,可能会影响研究结果。另一方面,技术方面,包括研究设计、放射性配体的限制或 PET 成像定量方法,可能会影响研究结果,应加以考虑以解释结果的差异。
SUD 的假定神经免疫成分提供了新的治疗方法,可用于预测和治疗 SUD,指出了中枢免疫信号的重要性。