de Jong T R, Pattij T, Veening J G, Dederen P J W C, Waldinger M D, Cools A R, Olivier B
Department of Anatomy, Radboud University Nijmegen Medical Centre, The Netherlands.
Neuroscience. 2005;134(4):1351-61. doi: 10.1016/j.neuroscience.2005.05.012.
Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. Male Wistar rats that were pretreated with paroxetine (20 mg/kg/day p.o.) or vehicle for 22 days and had received an additional injection with the 5-HT(1A) receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propyl-amino)tetralin; 0.4 mg/kg s.c.) or saline on day 22, 30 min prior to a sexual behavior test, were perfused 1 h after the sexual behavior test. Brains were processed for Fos-, and oxytocin immunohistochemistry. The drug treatments markedly changed both sexual behavior and the pattern and number of Fos-immunoreactive cells in the brain. Chronic pretreatment with paroxetine caused delayed ejaculation. Acute injection with 8-OH-DPAT facilitated ejaculation in vehicle-pretreated rats, notably evident in a strongly reduced intromission frequency, whereas 8-OH-DPAT had no effects in paroxetine-pretreated rats. Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects.
选择性5-羟色胺再摄取抑制剂帕罗西汀的长期治疗会损害参与射精的5-HT(1A)受体的功能。这可能是接受帕罗西汀治疗的男性常出现射精延迟的原因。研究了将选择性5-羟色胺再摄取抑制剂治疗的效果与5-HT(1A)受体激活和射精联系起来的神经生物学基础。雄性Wistar大鼠，预先用帕罗西汀（20毫克/千克/天，口服）或赋形剂处理22天，并在性行为测试前30分钟于第22天额外注射5-HT(1A)受体激动剂8-OH-DPAT（(+/-)-8-羟基-2-(二正丙基氨基)四氢萘；0.4毫克/千克，皮下注射）或生理盐水，在性行为测试后1小时进行灌注。对大脑进行Fos和催产素免疫组织化学处理。药物治疗显著改变了性行为以及大脑中Fos免疫反应性细胞的模式和数量。帕罗西汀的长期预处理导致射精延迟。对预先用赋形剂处理的大鼠急性注射8-OH-DPAT可促进射精，在插入频率大幅降低方面尤为明显，而8-OH-DPAT对预先用帕罗西汀处理的大鼠没有影响。帕罗西汀的长期治疗降低了蓝斑中的Fos免疫反应性，并阻止了8-OH-DPAT在室旁核催产素能大细胞部分以及蓝斑中诱导的Fos免疫反应性神经元的增加。由于催产素和去甲肾上腺素促进射精，这些区域Fos-IR的改变可能将选择性5-羟色胺再摄取抑制剂治疗和5-HT(1A)受体激活与射精联系起来。帕罗西汀的长期治疗和8-OH-DPAT改变了许多其他脑区的c-fos表达，表明Fos免疫组织化学是寻找选择性5-羟色胺再摄取抑制剂和8-OH-DPAT发挥作用部位的有用工具。
