The serotonin transporter plays an important role in male sexual behavior: a study in serotonin transporter knockout rats.
BACKGROUND
Serotonin (5-HT) is an important neurotransmitter for sexual behaviors. Heterozygous (+/-) serotonin transporter (SERT) rats and SERT knockout rats (-/-) have serotonergic disturbances with significant elevations of basal extracellular 5-HT levels.


OBJECTIVE
To investigate the putative role of the SERT in male sexual behavior.


METHODS
After extensive sexual training, the effects of the 5-HT(1A/7) receptor agonist ± 8-OH-DPAT, the 5-HT(1A) receptor antagonist WAY100 635 and a combination of both on sexual behaviors of SERT(-/-) and SERT(+/-) knockout and wildtype (SERT(+/+) ) male Wistar rats were examined.


METHODS
Male rat sexual behaviors of mounts, intromissions, and ejaculations.


RESULTS
SERT(-/-) had lower basal ejaculation frequencies than SERT(+/-) and SERT(+/+) animals. ± 8-OH-DPAT enhanced sexual performance in all three genotypes to the same extent. WAY100635 dose-dependently inhibited sexual behavior in all three genotypes with significant dose to genotype interactions. WAY100635 exerted the strongest effects in SERT(-/-) animals. The combination of a dose range of ± 8-OH-DPAT and a selected dose of WAY100635 revealed only partial antagonism by ± 8-OH-DPAT of the sexual inhibitory effects of WAY100635.


CONCLUSIONS
Absence of the serotonin transporter reduces basal ejaculatory performance in male rats. Pharmacological experiments suggest that separate pools of 5-HT(1A) receptors regulate different aspects of sexual performance in male rats. 5-HT(7) receptors may play a minor role in the partial recovery of sexual behavior after combination of ± 8-OH-DPAT and WAY100635. The SERT(-/-) rat may be a model for chronic SSRI treatment, delayed ejaculation, anorgasmia, and/or low libido.
Chan
Johnny S W
JS
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan, Utrecht, The Netherlands. j.s.w.chan@uu.nl
Snoeren
Eelke M S
EM
Cuppen
Edwin
E
Waldinger
Marcel D
MD
Olivier
Berend
B
Oosting
Ronald S
RS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004542:Ejaculation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D055647:Rats, Transgenic; D012702:Serotonin Antagonists / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D012725:Sexual Behavior / Q000187:drug effects / Q000502:physiology*; D012726:Sexual Behavior, Animal; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced* / Q000503:physiopathology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide