Anderson J L
Life Sci. 1983 Apr 18;32(16):1791-801. doi: 10.1016/0024-3205(83)90056-5.
Early biochemical research on antidepressant treatments provided evidence that the treatments alter catecholaminergic and serotonergic activity. The mechanisms of action proposed by the resulting biogenic amine hypotheses of affective disorders, however, are not consistent with the delayed onset of therapeutic effects of antidepressant treatments nor with the acute effects of more recently developed antidepressant drugs. Recent investigation of chronic antidepressant treatments using ligand binding, electrophysiological, and behavioral techniques have attempted to identify subgroups of receptors that might be affected uniquely and specifically by chronic antidepressant treatments. Such receptor changes have been suggested to form a basis for the mechanism of action of antidepressants. At the present time, however, the data produced by ligand binding experiments and electrophysiological experiments investigating serotonergic functioning do not fit together. In addition, interpretational problems and internal contradictions exist within each of the three bodies of data when straightforward hypotheses regarding a serotonergic role in antidepressant treatment are formulated. In order to clarify the serotonergic role in antidepressant drug and ECS effects the functional significance of observed changes in putative serotonergic receptors must be discovered. Unfortunately, putative receptors identified by ligand binding cannot be directly compared to those identified by electrophysiological techniques, because these two methods require the disassembly of the organism in mutually incompatible ways. In order to prove that either or both techniques do in fact identify functional serotonin receptors, investigators need to proceed both more microscopically and also more globally. Further anatomical and physiological studies are necessary to locate putative receptors and to demonstrate their place in existing serotonergic networks. Further behavioral studies must be done to relate alterations in receptor characteristics to the functioning of the intact organism.
早期关于抗抑郁治疗的生化研究表明，这些治疗会改变儿茶酚胺能和5-羟色胺能活性。然而，由此产生的情感障碍生物胺假说所提出的作用机制，与抗抑郁治疗的治疗效果延迟起效以及与最近开发的抗抑郁药物的急性效应均不一致。最近使用配体结合、电生理和行为技术对慢性抗抑郁治疗进行的研究，试图确定可能受到慢性抗抑郁治疗独特且特异性影响的受体亚组。有人认为这种受体变化构成了抗抑郁药作用机制的基础。然而，目前，研究5-羟色胺能功能的配体结合实验和电生理实验所产生的数据并不吻合。此外，当就5-羟色胺在抗抑郁治疗中的作用提出直接假设时，这三组数据中的每一组都存在解释问题和内部矛盾。为了阐明5-羟色胺在抗抑郁药物和电休克治疗效果中的作用，必须发现假定的5-羟色胺能受体中观察到的变化的功能意义。不幸的是，通过配体结合鉴定的假定受体无法直接与通过电生理技术鉴定的受体进行比较，因为这两种方法需要以相互不兼容的方式拆解生物体。为了证明这两种技术中的任何一种或两者实际上都能鉴定出功能性5-羟色胺受体，研究人员需要在更微观和更宏观的层面上开展工作。需要进一步的解剖学和生理学研究来定位假定的受体，并证明它们在现有的5-羟色胺能网络中的位置。必须进行进一步的行为研究，以将受体特征的改变与完整生物体的功能联系起来。
