Lithium is an effective drug for both treatment and prophylaxis of bipolar disorder. However, the mechanism of lithium action is still unknown. The inositol depletion hypothesis is supported by biochemical and behavioral data in rats, but primate inositol levels are higher than in rodents and may obviate the effects of depletion. Inhibition of 5HT autoreceptors by lithium is supported by biochemical and behavioral data in rats but would seem more related to lithium's antidepressant than to its antimanic or prophylactic effects. Lithium induces increases in levels of the anti-apoptotic factor Bcl-2. This effect could be most relevant for treatment of neurodegenerative disorders. Lithium inhibits glycogen synthase kinase-3, which is involved in a wide range of signal transduction pathways. However, this lithium effect occurs at high concentrations and may be more relevant for its toxic effect. Lithium in low concentrations induces accumulation of PAP, which affects several cellular processes including RNA processing. However, PAP phosphatase is present more in peripheral tissues than in brain. This lithium effect could explain some of its peripheral side effects. Chronic lithium administration upregulates glutamate reuptake and thus decreases glutamate availability in synapse. Glutamate is an excitatory neurotransmitter and its reduction could exert an antimanic effect. Biochemical and clinical experiments are necessary to determine the key mechanism of lithium efficacy in treatment and prophylaxis of affective disorders.

中文翻译：

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锂作用机理：十年后的最新技术。

锂是治疗和预防躁郁症的有效药物。但是，锂的作用机理仍然未知。大鼠生化和行为数据支持了肌醇耗竭假说，但是灵长类动物的肌醇水平高于啮齿动物，并且可以消除耗竭的影响。锂对5HT自身受体的抑制作用受到大鼠生化和行为数据的支持，但似乎与锂的抗抑郁药有关，而不是与其抗躁狂或预防作用有关。锂诱导抗凋亡因子Bcl-2水平升高。这种作用可能与神经退行性疾病的治疗最相关。锂抑制糖原合酶激酶3，该酶参与多种信号转导途径。然而，这种锂效应在高浓度下发生，可能与其毒性效应更为相关。低浓度的锂会诱导PAP积累，从而影响包括RNA加工在内的多个细胞过程。但是，PAP磷酸酶在外周组织中的含量要高于大脑。这种锂效应可以解释其一些外围副作用。长期服用锂会上调谷氨酸的再摄取，从而降低突触中谷氨酸的利用率。谷氨酸盐是一种兴奋性神经递质，其减少可产生抗躁狂作用。生化和临床实验对于确定锂疗效和预防情感障碍的关键机制是必要的。这会影响包括RNA加工在内的几个细胞过程。但是，PAP磷酸酶在外周组织中的含量要高于大脑。这种锂效应可以解释其一些外围副作用。长期服用锂会上调谷氨酸的再摄取，从而降低突触中谷氨酸的利用率。谷氨酸盐是一种兴奋性神经递质，其减少可产生抗躁狂作用。生化和临床实验对于确定锂疗效和预防情感障碍的关键机制是必要的。这会影响包括RNA加工在内的几个细胞过程。但是，PAP磷酸酶在外周组织中的含量要高于大脑。这种锂效应可以解释其一些外围副作用。长期服用锂会上调谷氨酸的再摄取，从而降低突触中谷氨酸的利用率。谷氨酸盐是一种兴奋性神经递质，其减少可产生抗躁狂作用。生化和临床实验对于确定锂疗效和预防情感障碍的关键机制是必要的。长期服用锂会上调谷氨酸的再摄取，从而降低突触中谷氨酸的利用率。谷氨酸盐是一种兴奋性神经递质，其减少可产生抗躁狂作用。生化和临床实验对于确定锂疗效和预防情感障碍的关键机制是必要的。长期服用锂会上调谷氨酸的再摄取，从而降低突触中谷氨酸的利用率。谷氨酸盐是一种兴奋性神经递质，其减少可产生抗躁狂作用。生化和临床实验对于确定锂疗效和预防情感障碍的关键机制是必要的。