Pettorruso Mauro, Zoratto Francesca, Miuli Andrea, De Risio Luisa, Santorelli Mario, Pierotti Alice, Martinotti Giovanni, Adriani Walter, di Giannantonio Massimo
Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11, I-66100, Chieti, Italy.
Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161, Rome, Italy.
Neurosci Biobehav Rev. 2020 Dec;119:481-511. doi: 10.1016/j.neubiorev.2020.09.034. Epub 2020 Oct 6.
Dopamine has a crucial and well-documented role in the development and maintenance of Gambling Disorder (GD). This systematic review adopts a translational approach aimed at providing a comprehensive synthesis of current clinical and preclinical knowledge on dopaminergic function in GD at a neurobiological level. To this end, we present and discuss converging dopaminergic alterations and phenotypes. Preclinical and clinical review protocols were registered on the PROSPERO database (CRD42019124404, CRD42019124405). The literature search was conducted in accordance with PRISMA guidelines using three databases (PubMed, Web of Science, Scopus). We identified 67 preclinical studies using pharmacological and non-pharmacological manipulations of the gambling-like phenotype and 33 human studies investigating either genetic polymorphisms or functional brain imaging data. Dopamine transporter and D2, D3, D4 receptor alterations showed strongest translational concordance. Though no postsynaptic dopaminergic alterations were observed, several studies point at dysfunctions in presynaptic dopamine trafficking in GD, suggestive of hyperdopaminergic states. Developing meaningful translational models is essential to working towards the development of an integrated conceptual framework for GD and neurobiologically-based treatment interventions.
多巴胺在赌博障碍（GD）的发展和维持中起着至关重要且有充分文献记载的作用。本系统综述采用一种转化方法，旨在在神经生物学层面全面综合当前关于GD中多巴胺能功能的临床和临床前知识。为此，我们展示并讨论了趋同的多巴胺能改变和表型。临床前和临床综述方案已在PROSPERO数据库（CRD42019124404，CRD42019124405）上注册。文献检索按照PRISMA指南使用三个数据库（PubMed、科学网、Scopus）进行。我们鉴定出67项使用类似赌博表型的药理学和非药理学操作的临床前研究，以及33项调查基因多态性或功能性脑成像数据的人体研究。多巴胺转运体以及D2、D3、D4受体的改变显示出最强的转化一致性。尽管未观察到突触后多巴胺能改变，但多项研究指出GD中突触前多巴胺转运存在功能障碍，提示多巴胺能亢进状态。开发有意义的转化模型对于努力构建GD的综合概念框架和基于神经生物学的治疗干预措施至关重要。
