Expanding the therapeutic potential of neuro(active)steroids: a promising strategy for hyperdopaminergic behavioral phenotypes

IF 7.5 1区医学 Q1 BEHAVIORAL SCIENCES

Neuroscience and Biobehavioral Reviews Pub Date : 2024-08-03 DOI:10.1016/j.neubiorev.2024.105842

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Abstract

Imbalances in dopamine activity significantly contribute to the pathophysiology of several neuropsychiatric disorders, including addiction, ADHD, schizophrenia, impulse control disorders, and Parkinson’s Disease. Neuro(active)steroids, comprising endogenous steroids that finely modulate neuronal activity, are considered crucial regulators of brain function and behavior, with implications in various physiological processes and pathological conditions. Specifically, subclasses of Neuro(active)steroids belonging to the 5α reductase pathway are prominently involved in brain disorders characterized by dopaminergic signaling imbalances. This review highlights the neuromodulatory effects of Neuro(active)steroids on the dopamine system and related aberrant behavioral phenotypes. We critically appraise the role of pregnenolone, progesterone, and allopregnanolone on dopamine signaling. Additionally, we discuss the impact of pharmacological interventions targeting 5α reductase activity in neuropsychiatric conditions characterized by excessive activation of the dopaminergic system, ranging from psychotic (endo)phenotypes and motor complications to decision-making problems and addiction.

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拓展神经（活性）类固醇的治疗潜力：治疗多巴胺能亢进行为表型的可行策略。

多巴胺活性失衡是多种神经精神疾病的重要病理生理因素，包括成瘾、多动症、精神分裂症、冲动控制障碍和帕金森病。神经（活性）类固醇包括能精细调节神经元活动的内源性类固醇，被认为是大脑功能和行为的重要调节剂，对各种生理过程和病理状况都有影响。具体而言，属于5α还原酶途径的神经（活性）类固醇亚类主要涉及以多巴胺能信号失衡为特征的脑部疾病。本综述强调了神经（活性）类固醇对多巴胺系统的神经调节作用以及相关的异常行为表型。我们严格评估了孕烯醇酮、孕酮和异丙孕酮对多巴胺信号传导的作用。此外，我们还讨论了针对 5α 还原酶活性的药物干预对以多巴胺能系统过度激活为特征的神经精神疾病的影响，这些疾病包括精神病（内）表型和运动并发症，以及决策问题和成瘾。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience and Biobehavioral Reviews 医学-行为科学

CiteScore

14.20

自引率

3.70%

发文量

466

审稿时长

6 months

期刊介绍： The official journal of the International Behavioral Neuroscience Society publishes original and significant review articles that explore the intersection between neuroscience and the study of psychological processes and behavior. The journal also welcomes articles that primarily focus on psychological processes and behavior, as long as they have relevance to one or more areas of neuroscience.