Chronic administration of venlafaxine fails to attenuate 5-HT1A receptor function at the level of receptor-G protein interaction.
Chronic administration of venlafaxine fails to attenuate 5-HT1A receptor function at the level of receptor-G protein interaction.
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DOI：
10.1017/s1461145705005754
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发表时间：
2006-08
期刊：
影响因子：
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通讯作者：
Dania V. Rossi;M. Valdez;G. Gould;J. Hensler
中科院分区：
文献类型：
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作者：
Dania V. Rossi;M. Valdez;G. Gould;J. Hensler
在这项研究中，文拉法辛以低、中或高剂量给予大鼠。为了进行比较，还包括选择性血清素再摄取抑制剂（SSRI）舍曲林和三环类抗抑郁药（TCA）阿米替林。我们使用定量放射自显影术评估了这些抗抑郁药物治疗对 5-HT1A 受体激动剂 8-OH-DPAT 刺激的 [35S]GTPgammaS 结合的影响，这是衡量 5-HT1A 受体激活 G 蛋白能力的指标。长期服用阿米替林导致海马中 5-HT1A 受体刺激的 [35S]GTPgammaS 结合显着增加，同时伴随着 5-HT1A 受体数量的增加。通过使用最高剂量的文拉法辛长期治疗，海马中 5-HT1A 受体刺激的 [35S]GTPgammaS 结合也增加；然而，5-HT1A 受体数量没有显着改变。在血清素能细胞体区域（即中缝核和中缝核），长期服用阿米替林、舍曲林或文拉法辛不会改变 5-HT1A 受体刺激的 [35S]GTPgammaS 结合。慢性 TCA 治疗不会使体细胞树突 5-HT1A 自身受体功能脱敏。然而，长期舍曲林治疗对 5-HT1A 受体刺激的 [35S]GTPgammaS 结合缺乏作用，这与之前长期服用 SSRI 氟西汀后观察到的情况形成鲜明对比，这表明不同的 SSRI 可能根据其药理学不同地调节体细胞树突状 5-HT1A 自身受体功能。我们的数据还表明，在长期服用文拉法辛后的电生理研究中观察到的体细胞树突 5-HT1A 自身受体的脱敏并不处于受体-G 蛋白相互作用的水平。用文拉法辛或舍曲林（而非阿米替林）长期治疗后，体内对急性注射 8-OH-DPAT 的低温反应显着减弱。
In this study venlafaxine was administered to rats at a low, moderate or high dose; for comparison, the selective serotonin reuptake inhibitor (SSRI) sertraline and the tricyclic antidepressant (TCA) amitriptyline were also included. We evaluated, using quantitative autoradiography, the effect of these antidepressant treatments on [35S]GTPgammaS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT, a measure of the capacity of 5-HT1A receptors to activate G proteins. Chronic administration of amitriptyline resulted in a marked increase in 5-HT1A receptor-stimulated [35S]GTPgammaS binding in the hippocampus which was accompanied by an increase in 5-HT1A receptor number. 5-HT1A receptor-stimulated [35S]GTPgammaS binding in the hippocampus was also increased by chronic treatment with the highest dose of venlafaxine; 5-HT1A receptor number, however, was not significantly altered. In serotonergic cell body areas (i.e. dorsal and median raphe nuclei), 5-HT1A receptor-stimulated [35S]GTPgammaS binding was not altered by chronic administration of amitriptyline, sertraline or venlafaxine. Chronic TCA treatment does not desensitize somatodendritic 5-HT1A autoreceptor function. However, the lack of effect of chronic sertraline treatment on 5-HT1A receptor-stimulated [35S]GTPgammaS binding is in contrast to what has been observed previously following chronic administration of the SSRI fluoxetine, and suggests that different SSRIs may regulate somatodendritic 5-HT1A autoreceptor function differently depending on their pharmacology. Our data also suggest that the desensitization of somatodendritic 5-HT1A autoreceptors observed in electrophysiological studies following chronic venlafaxine administration is not at the level of receptor-G protein interaction. The hypothermic response in vivo to acute injection of 8-OH-DPAT was significantly attenuated following chronic treatment with venlafaxine or sertraline, but not amitriptyline.