Chan Johnny S W, Olivier Berend, de Jong Trynke R, Snoeren Eelke M S, Kooijman Elke, van Hasselt Felisa N, Limpens Jules H W, Kas Martien J H, Waldinger Marcel D, Oosting Ronald S
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands. address:
Eur J Pharmacol. 2008 May 13;585(2-3):426-35. doi: 10.1016/j.ejphar.2008.02.098. Epub 2008 Mar 18.
The existence of sexual dysfunctions in men, including premature and retarded ejaculation poses challenges to develop translational models in rats that may help in improving treatment and delineate the neural mechanisms of action. Most of our current understanding of the neurobiology, neuroanatomy and psychopharmacology of sexual behavior and ejaculatory function has been derived from preclinical studies in the rat. When large populations of male rats are tested on sexual activity during four successive tests, over time individual rats display a very stable sexual behavior that is either slow, normal or fast as characterized by the number of ejaculations performed. These sexual endophenotypes are postulated as rat counterparts of premature (fast rats) or retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes may help to delineate the underlying mechanisms and pathology. This is illustrated by the effects of serotonergic antidepressants and serotonergic compounds on sexual and ejaculatory behavior of rats. Further unravelling of sexual endophenotypes may benefit from the use of chromosomal substitution strains in mice that enable the localization of relevant chromosomal areas and genes involved in ejaculation processes. These preclinical studies and models contribute to a better understanding of the neurobiology of ejaculation and boost the development of novel drug targets to treat ejaculatory disorders such as premature and retarded ejaculation.
男性性功能障碍的存在，包括早泄和射精延迟，对在大鼠中开发转化模型构成了挑战，这些模型可能有助于改善治疗并阐明其神经作用机制。我们目前对性行为和射精功能的神经生物学、神经解剖学和精神药理学的大多数理解都来自于对大鼠的临床前研究。当大量雄性大鼠在连续四次测试中接受性行为测试时，随着时间的推移，个体大鼠会表现出非常稳定的性行为，根据射精次数的多少，性行为要么缓慢、正常，要么快速。这些性内表型被假定为早泄（快大鼠）或射精延迟（慢大鼠）的大鼠对应物。这些内表型的精神药理学可能有助于阐明潜在的机制和病理。血清素能抗抑郁药和血清素能化合物对大鼠性行为和射精行为的影响就说明了这一点。进一步揭示性内表型可能受益于在小鼠中使用染色体替代品系，这能够定位参与射精过程的相关染色体区域和基因。这些临床前研究和模型有助于更好地理解射精的神经生物学，并推动开发治疗射精障碍如早泄和射精延迟的新型药物靶点。
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