Goodwin G M, De Souza R J, Green A R
Nature. 1985;317(6037):531-3. doi: 10.1038/317531a0.
Ligand-binding studies have demonstrated two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the brains of rodents and there is additional evidence for the existence of 5-HT1 subtypes. Recently a new drug, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), has been identified which shows high selectivity for binding to 5-HT1 (possibly 5-HT1A) receptors and which binds to presynaptic serotonin autoreceptors in some regions of rat brain. We have shown previously, that this compound produces a hypothermic response in mice, probably via an agonist action at serotonin presynaptic receptors. Here we show that a wide range of antidepressant treatments decrease the hypothermic response to 8-OH-DPAT over a time course comparable to the onset of therapeutic action. Interestingly, repeated electroconvulsive shock (ECS) has the same effect. We propose that this change is relevant to the mechanism of action of antidepressant drugs.
配体结合研究已在啮齿动物大脑中证实存在两种类型的5-羟色胺（5-HT）受体，即5-HT1和5-HT2，并且有更多证据表明存在5-HT1亚型。最近发现了一种新药，8-羟基-2-（二-N-丙基氨基）四氢萘（8-OH-DPAT），它对5-HT1（可能是5-HT1A）受体具有高选择性，并且能与大鼠脑某些区域的突触前5-羟色胺自身受体结合。我们之前已经表明，该化合物在小鼠中会产生体温降低反应，可能是通过对5-羟色胺突触前受体的激动作用。在此我们表明，一系列抗抑郁治疗在与治疗作用起效相当的时间进程中会降低对8-OH-DPAT的体温降低反应。有趣的是，重复电休克（ECS）也有相同效果。我们提出这种变化与抗抑郁药物的作用机制相关。
