A desensitization of hypothalamic 5-HT1A receptors by repeated injections of paroxetine: reduction in the levels of G(i) and G(o) proteins and neuroendocrine responses, but not in the density of 5-HT1A receptors.
A desensitization of hypothalamic 5-HT1A receptors by repeated injections of paroxetine: reduction in the levels of G(i) and G(o) proteins and neuroendocrine responses, but not in the density of 5-HT1A receptors.
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发表时间：
1997-09
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通讯作者：
Qian Li;N. Muma;George Battaglia;L. Kar
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作者：
Qian Li;N. Muma;George Battaglia;L. Kar
本研究的目的是确定是否先前观察到的脱敏下丘脑5-羟色胺1A（5-HT1A）受体，在每日注射氟西汀，介导的持续封锁5-HT再摄取。在本研究中，我们研究了另一种5-HT摄取抑制剂帕罗西汀的时程效应。帕罗西汀减少催产素，肾上腺皮质激素和皮质酮的反应，以5-HT1A激动剂8-羟基-2-（二丙氨基）四氢萘的挑战。这些激素反应的降低在每天注射3次后是显著的，并且在每天注射7次帕罗西汀后达到最大值。这些激素反应在每天注射帕罗西汀14次后仍然受到最大程度的抑制。一天的帕罗西汀治疗没有改变对8-羟基-2-（二丙氨基）四氢萘的激素反应。重复注射帕罗西汀并没有降低任何脑区5-HT1A受体的密度，但确实以区域特异性的方式逐渐降低了G（i）和G（o）蛋白的水平。帕罗西汀诱导的下丘脑G（i1）和G（i3）蛋白水平降低的时间过程与先前用氟西汀观察到的效果相似，也与帕罗西汀诱导的催产素和促肾上腺皮质激素对8-羟基-2-（二丙氨基）四氢萘反应降低的时间过程相似。总之，这些结果表明，5-HT摄取位点的封锁产生延迟和逐渐脱敏的5-HT 1A受体在下丘脑。这种脱敏不是由于下丘脑5-HT1A受体密度的变化。下丘脑G（i3）蛋白水平的降低可能在5-HT 1A受体系统的脱敏中起作用。然而，G（i1）或G（o）蛋白的减少不能被排除作为5-HT1A受体系统脱敏的潜在介质。
The aim of the present study was to determine whether the previously observed desensitization of hypothalamic 5-hydroxytryptamine1A (5-HT1A) receptors, during daily injections of fluoxetine, is mediated by sustained blockade of 5-HT reuptake. In the present study, we examined the time course effects of another 5-HT uptake inhibitor, paroxetine. Paroxetine reduced the oxytocin, adrenal corticotropic hormone and corticosterone responses to a challenge with the 5-HT1A agonist 8-hydroxy-2-(dipropylamino)tetralin. These reductions in hormone responses were significant after 3 daily injections and reached a maximum after 7 daily paroxetine injections. These hormone responses remained maximally suppressed after 14 daily injections of paroxetine. A single day of paroxetine treatment did not alter the hormone responses to 8-hydroxy-2-(dipropylamino)tetralin. Repeated injections of paroxetine did not reduce the density of 5-HT1A receptors in any brain region but did produce a gradual reduction in the levels of G(i) and G(o) proteins in a region-specific manner. The time course of the paroxetine-induced reduction in the level of G(i1) and G(i3) proteins in the hypothalamus was similar to the effect previously observed with fluoxetine and was also similar to the time course of paroxetine-induced reductions in oxytocin and adrenal corticotropic hormone responses to 8-hydroxy-2-(dipropylamino)tetralin. In conclusion, these results suggest that blockade of 5-HT uptake sites produces a delayed and gradual desensitization of 5-HT1A receptors in the hypothalamus. This desensitization is not due to changes in the density of hypothalamic 5-HT1A receptors. Reduction in the hypothalamic level of G(i3) proteins may play a role in the desensitization of 5-HT1A receptor systems. However, reductions in G(i1) or G(o) proteins cannot be excluded as potential mediators of the desensitization of 5-HT1A receptor systems.