Owens M J, Ballenger C A, Knight D L, Nemeroff C B
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
J Pharmacol Exp Ther. 1996 Sep;278(3):1040-9.
There is considerable evidence that the number of platelet 5-hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5-HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I] (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT2A receptor binding. Similarly, 8-week administration of the 5-HT2A/5-HT2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT2A/2C receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT2A receptors. Additionally, para-chloroamphetamine-(11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT2A receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT2A receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status.
有大量证据表明，在未服用药物的重度抑郁症患者中，通过[3H]丙咪嗪结合测定的血小板5-羟色胺（5-HT）转运体结合位点数量显著减少，而血小板5-HT2受体密度增加。为了研究血小板5-HT转运体或5-HT2受体位点的这些变化是否源于重度抑郁症中已知或假设的生化变化，我们在大鼠中检查了慢性高糖皮质激素状态，或中枢神经系统5-HT神经传递的减少或增加，是否分别改变了选择性配体[3H]西酞普兰和[125I]（+/-）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷与血小板和脑5-HT转运体及5-HT2受体的结合。慢性（6周）高皮质酮血症并未改变脑或血小板5-HT转运体或5-HT2A受体结合。同样，以下调脑5-HT2A/2C受体的剂量给予5-HT2A/5-HT2C激动剂（+/-）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷8周，并未改变脑或血小板5-HT转运体或血小板5-HT2A受体。此外，对氯苯丙胺（11周）或芬氟拉明诱导的中枢神经系统5-HT慢性（1.5 - 10周）耗竭并未改变血小板5-HT转运体或5-HT2A受体结合。最后，在任何对照组或治疗组中，脑和血小板中5-HT转运体的数量之间均无相关性。这些发现表明，抑郁症患者血小板5-HT转运体和5-HT2A受体结合的观察到的变化更可能源于遗传（即性状依赖性），而非高皮质醇血症或中枢神经系统5-HT状态改变的附带现象。
