The prevention and treatment of addiction (moderate to severe substance use disorder—SUD) have remained challenging because of the dynamic and complex interactions between multiple biological and social determinants that shape SUD. The pharmacological landscape is ever changing and the use of multiple drugs is increasingly common, requiring an unraveling of pharmacological interactions to understand the effects. There are different stages in the trajectory from drug use to addiction that are characterized by distinct cognitive and emotional features. These are directed by different neurobiological processes that require identification and characterization including those that underlie the high co-morbidity with other disorders. Finally, there is substantial individual variability in the susceptibility to develop SUD because there are multiple determinants, including genetics, sex, developmental trajectories and times of drug exposures, and psychosocial and environmental factors including commercial determinants that influence drug availability. Elucidating how these factors interact to determine risk is essential for identifying the biobehavioral basis of addiction and developing prevention and treatment strategies. Basic research is tasked with addressing each of these challenges. The recent proliferation of technological advances that allow for genetic manipulation, visualization of molecular reactions and cellular activity in vivo, multiscale whole brain mapping across the life span, and the mining of massive data sets including multimodality human brain imaging are accelerating our ability to understand how the brain functions and how drugs influence it. Here, we highlight how the application of these tools to the study of addiction promises to illuminate its neurobiological basis and guide strategies for prevention and treatment.

由于形成 SUD 的多个生物和社会决定因素之间动态且复杂的相互作用，成瘾（中度至重度物质使用障碍 - SUD）的预防和治疗仍然具有挑战性。药理学格局不断变化，多种药物的使用越来越普遍，需要阐明药理学相互作用以了解其效果。从吸毒到成瘾的轨迹有不同的阶段，其特点是不同的认知和情感特征。这些是由不同的神经生物学过程指导的，需要识别和表征，包括那些与其他疾病高共发病率的基础的神经生物学过程。最后，发展 SUD 的易感性存在很大的个体差异，因为存在多种决定因素，包括遗传、性别、发育轨迹和药物暴露时间，以及社会心理和环境因素，包括影响药物可用性的商业决定因素。阐明这些因素如何相互作用以确定风险对于确定成瘾的生物行为基础并制定预防和治疗策略至关重要。基础研究的任务是解决这些挑战。最近技术进步的激增，允许基因操作、体内分子反应和细胞活动的可视化、整个生命周期的多尺度全脑绘图，以及包括多模态人脑成像在内的海量数据集的挖掘，正在加速我们理解如何大脑功能以及药物如何影响它。在这里，我们强调这些工具在成瘾研究中的应用如何有望阐明其神经生物学基础并指导预防和治疗策略。