Pelvipharm Laboratories, Orsay, France.
J Sex Med. 2012 Oct;9(10):2562-73. doi: 10.1111/j.1743-6109.2012.02884.x. Epub 2012 Aug 20.
A brain network specifically activated when ejaculation occurs has been described in rats. Increasing serotonin (5-hydroxytryptamine [5-HT]) tone impairs ejaculation and chronic 5-HT selective serotonin reuptake inhibitors (SSRIs) are known to inhibit ejaculation. However, efficacy of acute treatment with SSRI varies from one compound to another. The SSRI dapoxetine has been reported to delay ejaculation when given on demand to men with premature ejaculation (PE), although the mechanism of action is unclear. Effects of acute SSRIs on activity of the brain ejaculation circuit in relation with ejaculation have never been examined.
To test the effects of acute administration of the short half-life SSRI dapoxetine on ejaculatory performance and activity in brain ejaculation circuit in rapid ejaculator rats taken as PE model.
Standard copulatory test was used to attribute one sexual category (sluggish, middle, or rapid) to male rats on the basis of their ejaculatory performance. Parameters of sexual, including ejaculatory, behavior, and Fos level of expression in discrete brain areas were assessed in the three sexual categories and in rapid category following acute oral treatment with dapoxetine.
Ejaculation frequency (EF) and latency (EL) were measured as primary end points of ejaculatory behavior. Density of Fos-immunopositive cells in specific brain areas of brain stem, hypothalamus, and thalamus was determined as marker of neuronal activity.
EL and Fos level of expression in hypothalamic and thalamic structures were found related. Dapoxetine acute oral administration (300 mg/kg) to rapid ejaculator rats resulted in (i) diminution of ejaculatory performance (lengthened EL and decreased EF); and (ii) modulation of Fos level of expression in hypothalamic and thalamic nuclei of the brain ejaculatory circuit.
Acute treatment with dapoxetine, which reduced ejaculatory performance in rapid ejaculator rats, was also accompanied with changes in neuronal activity in components of the brain ejaculatory network.
在大鼠中描述了一种专门在射精时激活的大脑网络。增加 5-羟色胺（5-羟色胺[5-HT]）的张力会损害射精，而慢性 5-HT 选择性 5-羟色胺再摄取抑制剂（SSRIs）已知可抑制射精。然而，不同化合物的 SSRIs 急性治疗的疗效有所不同。据报道，SSRIs 达泊西汀按需给予早泄（PE）男性可延迟射精，尽管作用机制尚不清楚。急性 SSRIs 对与射精相关的大脑射精回路活动的影响从未被检查过。
测试短半衰期 SSRIs 达泊西汀的急性给药对快速射精大鼠的射精表现和大脑射精回路活动的影响，这些大鼠被认为是 PE 模型。
根据雄性大鼠的射精表现，通过标准交配试验将其归为一种性类别（缓慢、中等或快速）。在三个性类别中评估了性行为参数，包括射精行为，以及在急性口服达泊西汀后快速类别中的脑区 Fos 表达水平。
射精频率（EF）和潜伏期（EL）作为射精行为的主要终点进行测量。特定脑区的 Fos 免疫阳性细胞密度确定为神经元活动的标志物。
发现 EL 和下丘脑和丘脑结构中的 Fos 表达水平相关。急性口服达泊西汀（300mg/kg）给予快速射精大鼠导致（i）射精表现降低（延长 EL 和减少 EF）；和（ii）大脑射精回路的下丘脑和丘脑核中的 Fos 表达水平发生变化。
急性治疗达泊西汀可降低快速射精大鼠的射精性能，同时还伴有大脑射精网络成分中神经元活动的变化。
