Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Rajasthan 333031, India.
Neurosci Biobehav Rev. 2016 May;64:311-25. doi: 10.1016/j.neubiorev.2016.03.001. Epub 2016 Mar 11.
5HT3 receptors (5HT3Rs) have long been identified as a potential target for antidepressants. Several studies have reported that antagonism of 5HT3Rs produces antidepressant-like effects. However, the exact role of 5HT3Rs and the mode of antidepressant action of 5HT3R antagonists still remain a mystery. Here, we provide a comprehensive overview of 5HT3Rs: (a) regional and subcellular distribution of 5HT3Rs in discrete brain regions, (b) preclinical and clinical evidence supporting the antidepressant effect of 5HT3R antagonists, and (c) neurochemical, biological and neurocellular signaling pathways associated with the antidepressant action of 5HT3R antagonists. 5HT3Rs located on the serotonergic and other neurotransmitter interneuronal projections control their release and affect mood and emotional behavior; however, new evidence suggests that apart from modulating the neurotransmitter functions, 5HT3R antagonists have protective effects in the pathogenic events including hypothalamic-pituitary-adrenal-axis hyperactivity, brain oxidative stress and impaired neuronal plasticity, pointing to hereby unknown and novel mechanisms of their antidepressant action. Nonetheless, further investigations are warranted to establish the exact role of 5HT3Rs in depression and antidepressant action of 5HT3R antagonists.
5-HT3 受体（5HT3Rs）长期以来一直被认为是抗抑郁药的潜在靶点。多项研究报告称，拮抗 5HT3Rs 可产生抗抑郁样作用。然而，5HT3Rs 的确切作用以及 5HT3R 拮抗剂的抗抑郁作用模式仍然是一个谜。在这里，我们提供了一个全面的 5HT3Rs 概述：（a）5HT3Rs 在离散脑区中的区域和亚细胞分布，（b）支持 5HT3R 拮抗剂抗抑郁作用的临床前和临床证据，以及（c）与 5HT3R 拮抗剂抗抑郁作用相关的神经化学、生物学和神经细胞信号通路。位于 5-HT 能和其他神经递质中间神经元投射上的 5HT3Rs 控制它们的释放，影响情绪和情绪行为；然而，新的证据表明，除了调节神经递质功能外，5HT3R 拮抗剂在包括下丘脑-垂体-肾上腺轴活性亢进、脑氧化应激和神经元可塑性受损在内的致病事件中具有保护作用，这表明它们具有未知的和新的抗抑郁作用机制。尽管如此，仍需要进一步的研究来确定 5HT3Rs 在抑郁症中的确切作用以及 5HT3R 拮抗剂的抗抑郁作用。
