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首页> 外文期刊>The journal of sexual medicine >Chronic paroxetine treatment does not affect sexual behavior in hormonally sub-primed female rats despite 5-HT(A) receptor desensitization.
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Chronic paroxetine treatment does not affect sexual behavior in hormonally sub-primed female rats despite 5-HT(A) receptor desensitization.

机译：尽管5-HT（A）受体脱敏，但慢性帕罗西汀治疗不会影响激素引发的雌性大鼠的性行为。

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INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) cause sexual dysfunctions in humans. However, because SSRIs are used to treat depression, it is unclear whether the problems are caused by the drug, by the depression itself, or an interaction between both. AIM: The present study investigated the effects of chronic paroxetine treatment on sexual behavior in female rats. Furthermore, we tested whether 5-hydroxytryptamine (5-HT)(A) receptors were desensitized in these females. METHODS: Ovariectomized female rats, either sub-primed with estradiol or fully primed with estradiol and progesterone, were tested in a paced mating test. Proceptive (darting and hopping), receptive (lordosis), and paced mating-related (percentages of exits and contact-return latencies) behaviors were quantified during the course of 56 days of chronic paroxetine treatment (10 mg/kg and 20 mg/kg per day). The 5-HT(A) /5-HT receptor agonist (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide ((+/-)8-OH-DPAT) alone and in combination with the selective 5-HT(A) receptor antagonist WAY-100635 was administered to study putative 5-HT(A) desensitization in the same females. MAIN OUTCOME MEASURES: Proceptive, receptive, and paced mating behaviors were quantified. RESULTS: Acute and chronic paroxetine treatment did not change proceptive and receptive behaviors in both sub-primed and fully primed female rats. In all groups, (+/-)8-OH-DPAT showed a clear dose-dependent inhibition of sexual behaviors in vehicle-treated females and a right-shifted dose-response effect in the paroxetine-treated rats. WAY-100635 attenuated the inhibiting effect of the 5-HT(A) receptor agonist in all females. These data suggest 5-HT(A) receptor desensitization after chronic paroxetine treatment. CONCLUSIONS: Chronic paroxetine treatment does not cause sexual side effects in sub- or fully hormonally primed female rats. Furthermore, chronic treatment causes adaptive changes in the serotonin system such as desensitization of 5-HT(A) receptors, which may counteract the inhibiting effects of increased extracellular serotonin levels in the chronic paroxetine-treated rats.
机译：简介：选择性5-羟色胺再摄取抑制剂（SSRIs）会导致人类的性功能障碍。但是，由于SSRI用于治疗抑郁症，因此尚不清楚问题是由药物引起的，还是由抑郁症本身引起的，还是由两者之间的相互作用引起的。目的：本研究调查了慢性帕罗西汀治疗对雌性大鼠性行为的影响。此外，我们测试了5-羟色胺（5-HT）（A）受体是否在这些女性中脱敏。方法：在有节律的交配试验中对卵巢切除的雌性大鼠进行雌雄激素预处理或完全雌二醇和孕激素预处理。在慢性帕罗西汀治疗56天（10 mg / kg和20 mg / kg）的过程中，对感受性（飞跃和跳跃），感受性（驼背）和与步伐相关的交配（退出和接触-返回潜伏期的百分比）行为进行了量化。每天）。 5-HT（A）/ 5-HT受体激动剂（+/-）-8-羟基-2-（二丙基氨基）四氢呋喃氢溴酸盐（（+/-）8-OH-DPAT）单独使用，并与选择性5给予-HT（A）受体拮抗剂WAY-100635，以研究同一女性中假定的5-HT（A）脱敏。主要观察指标：知觉，接受和有节奏的交配行为进行了量化。结果：急性和慢性帕罗西汀治疗均未改变初免和完全启动雌性大鼠的知觉和接受行为。在所有组中，（+/-）8-OH-DPAT在媒介物治疗的雌性动物中表现出明显的剂量依赖性抑制性行为，在帕罗西汀治疗的大鼠中显示出右移的剂量反应效应。 WAY-100635减弱了所有雌性动物中5-HT（A）受体激动剂的抑制作用。这些数据表明慢性帕罗西汀治疗后5-HT（A）受体脱敏。结论：慢性帕罗西汀治疗不会在激素不足或完全激素的雌性大鼠中引起性副作用。此外，慢性治疗引起5-羟色胺系统的适应性改变，例如5-HT（A）受体脱敏，这可能抵消了慢性帕罗西汀治疗大鼠的细胞外5-羟色胺水平升高的抑制作用。

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