Translational research into sexual disorders: pharmacology and genomics.
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.
Chan
Johnny S W
JS
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands. address: j.s.w.chan@uu.nl
Olivier
Berend
B
de Jong
Trynke R
TR
Snoeren
Eelke M S
EM
Kooijman
Elke
E
van Hasselt
Felisa N
FN
Limpens
Jules H W
JH
Kas
Martien J H
MJ
Waldinger
Marcel D
MD
Oosting
Ronald S
RS
D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology; D004542:Ejaculation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics*; D020018:Sexual Dysfunctions, Psychological / Q000188:drug therapy* / Q000235:genetics*
D000928:Antidepressive Agents; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors