Enhancing translation: A need to leverage complex preclinical models of addictive drugs to accelerate substance use treatment options

IF 3.3 3区 心理学 Q1 BEHAVIORAL SCIENCES Pharmacology Biochemistry and Behavior Pub Date : 2024-07-26 DOI:10.1016/j.pbb.2024.173836
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Abstract

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neurobehavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical experiences in individuals who use drugs. In this review, we provide a comprehensive update on both frequently utilized and novel behavioral models of addiction with a focus on translational value to the clinical experience and highlight the need for preclinical research to follow epidemiological trends in drug use patterns to stay abreast of clinical treatment needs. We then note areas in which models could be improved to enhance the medications development pipeline through efforts to enhance translation of preclinical models. Next, we describe neuroscience efforts that can be leveraged to identify novel biological mechanisms to enhance medications development efforts for SUDs, focusing specifically on advances in brain transcriptomics approaches that can provide comprehensive screening and identification of novel targets. Together, the confluence of this review demonstrates the need for careful selection of behavioral models and methodological parameters that better approximate the clinical experience combined with cutting edge neuroscience techniques to advance the medications development pipeline for SUDs.

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加强转化:需要利用复杂的成瘾药物临床前模型来加快药物使用治疗方案的制定。
几十年来,人们一直在开发成瘾药物的临床前模型,以模拟药物使用障碍(SUD)的临床经验。这些模型包括各种成瘾药物的被动暴露模型和自愿摄入模型,并被用于测量戒断症状和导致药物寻求或服用复发的潜在神经行为机制。美国食品和药物管理局 (FDA) 批准了许多治疗药物,但许多药物的临床疗效较低,而且存在潜在的性别差异。在这篇综述中,我们全面介绍了常用和新型成瘾行为模型的最新情况,重点关注这些模型对临床经验的转化价值,并强调临床前研究需要紧跟药物使用模式的流行病学趋势,以跟上临床治疗需求。然后,我们指出了可以改进模型的领域,以便通过加强临床前模型的转化工作来提高药物开发的质量。接下来,我们将介绍神经科学在识别新型生物机制方面所做的努力,以加强药物研发工作,特别是脑转录组学方法的进展,该方法可提供全面筛选和识别新型靶点的能力。综上所述,有必要谨慎选择行为模型和方法参数,以便更好地贴近临床经验,并结合最前沿的神经科学技术,推进药物研发工作。
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来源期刊
CiteScore
6.40
自引率
2.80%
发文量
122
审稿时长
38 days
期刊介绍: Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.
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