Beaulieu Jean-Martin, Caron Marc G
Department of Anatomy and Physiology, Université Laval/CRULRG, Québec, Canada G1J 2G3.
Mol Interv. 2008 Oct;8(5):230-41. doi: 10.1124/mi.8.5.8.
Lithium and other mood-stabilizing drugs are used for the management of bipolar mood disorders and, to a lesser extent, for augmentation of other psychoactive drugs. Lithium also has neuroprotective properties that may be useful for treatment of neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. Over the years, lithium has been shown to inhibit inositol monophosphatases and glycogen synthase kinase 3, but the relevance of such enzyme inhibition to the therapeutic effects of lithium has remained difficult to assess. Here, we provide an overview of recent advances in the identification of molecular mechanisms involved in the regulation of behavior by lithium. We also highlight recent findings suggesting that lithium could exert some of its behavioral effects by acting on a dopamine receptor regulated signaling complex composed of Akt, protein phosphatase 2A, and the multifunctional protein scaffold beta-arrestin 2.
锂盐及其他心境稳定剂用于治疗双相情感障碍，在较小程度上也用于增强其他精神活性药物的疗效。锂盐还具有神经保护特性，可能对治疗神经退行性疾病如阿尔茨海默病和肌萎缩侧索硬化症有用。多年来，锂盐已被证明可抑制肌醇单磷酸酶和糖原合酶激酶3，但这种酶抑制与锂盐治疗效果的相关性仍难以评估。在此，我们概述了锂盐调节行为所涉及分子机制鉴定方面的最新进展。我们还强调了最近的研究结果，这些结果表明锂盐可能通过作用于由Akt、蛋白磷酸酶2A和多功能蛋白支架β-抑制蛋白2组成的多巴胺受体调节信号复合物来发挥其部分行为效应。
