Olivier Jocelien D A, de Jong Trynke R, Jos Dederen P, van Oorschot Ruud, Heeren Dick, Pattij Tommy, Waldinger Marcel D, Coolen Lique M, Cools Alexander R, Olivier Berend, Veening Jan G
Department of Anatomy, UMC St Radboud, University of Nijmegen, The Netherlands.
Eur J Pharmacol. 2007 Dec 8;576(1-3):61-76. doi: 10.1016/j.ejphar.2007.08.019. Epub 2007 Aug 23.
Apomorphine is a non-selective dopaminergic receptor agonist. Because of its pro-erectile effects, apomorphine is clinically used for treatment of erectile dysfunction. We investigated the effects of subcutaneous apomorphine administration (0.4 mg/kg rat) on sexual behavior and mating-induced Fos-expression following acute (day 1) or chronic apomorphine treatment (days 8 and 15) in sexually experienced male rats. Consistent facilitatory effects of apomorphine were observed in the reduced numbers of mounts and intromissions over time and an increased ejaculation frequency on day 1. The first post-ejaculatory interval, however, was lengthened, while other behavioral parameters were unaffected. Fos-immunoreactivity induced by acute apomorphine administration (barrel cortex, paraventricular hypothalamic nucleus, central amygdala and locus coeruleus) was strongly reduced after chronic administration. After mating, induction of Fos-immunoreactivity was observed in well-known areas like medial preoptic nucleus and the posterodorsal medial amygdaloid area. Apomorphine, however, reduced mating-induced Fos-immunoreactivity in the nucleus accumbens shell and prevented its occurrence in its core area. This remarkable apomorphine effect was not observed in any other brain area. We conclude that the behavioral (pro-erectile) effects of apomorphine are consistent over time, and that the diminished accumbens-Fos-immunoreactivity and the elongated post-ejaculatory interval may reflect a decreased response to remote cues from the estrus female.
阿扑吗啡是一种非选择性多巴胺能受体激动剂。由于其促进勃起的作用,阿扑吗啡在临床上用于治疗勃起功能障碍。我们研究了在有性经验的雄性大鼠中,急性(第1天)或慢性阿扑吗啡治疗(第8天和第15天)后皮下注射阿扑吗啡(0.4mg/kg大鼠)对性行为和交配诱导的Fos表达的影响。随着时间的推移,观察到阿扑吗啡对 mounts和插入次数减少具有持续的促进作用,并且在第1天射精频率增加。然而,首次射精后间隔时间延长,而其他行为参数未受影响。急性注射阿扑吗啡诱导的Fos免疫反应性(桶状皮质、室旁下丘脑核、中央杏仁核和蓝斑)在慢性给药后显著降低。交配后,在如内侧视前核和后内侧杏仁核区域等知名区域观察到Fos免疫反应性的诱导。然而,阿扑吗啡降低了伏隔核壳中交配诱导的Fos免疫反应性,并阻止了其在核心区域的出现。在任何其他脑区均未观察到这种显著的阿扑吗啡效应。我们得出结论,阿扑吗啡的行为(促进勃起)效应随时间持续存在,伏隔核Fos免疫反应性降低和射精后间隔时间延长可能反映了对来自发情雌性的远距离线索反应的降低。