Olivier Prof. Jocelien D, Hogenbirk Jolijn, Stephen De Prêtre Stephen, Olivier Prof. Berend

(165) PAROXETINE COMBINED WITH ATLAS987 DOES NOT INHIBIT SEXUAL BEHAVIOR IN SEROTONIN TRANSPORTER KNOCKOUT RATS

  • Urology
  • Reproductive Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
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Abstract Objectives Enduro is a drug that combines paroxetine with the 5-HT1A-receptor antagonist Atlas987. In rats this drug successfully acutely inhibits the sexual behavior, making it relevant for on demand treatment of lifelong premature ejaculation in men. Because the serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the latency to ejaculate in men with premature ejaculation, we were interested to test this drug in an animal model without the serotonin transporter, the serotonin transporter knockout (SERT-/-) rat. We hypothesized that SERT-/- rats would not respond to an SSRI, but that the 5-HT1A-receptor antagonist Atlas987 would inhibit sexual behavior as previously shown with the reference 5-HT1A-receptor antagonist WAY100635. Methods Wildtype (SERT+/+) and SERT-/- male Wistar rats were trained in a 30-minute weekly sexual performance test, for ten weeks. Rats with a high number of ejaculations (10 SERT+/+ and 10 SERT-/-) were selected. Atlas987 (s.c.) was dose-dependently administered with either placebo (saline) or Paroxetine (10 mg/kg; i.p.). Acute responses on sexual behavior assessed in both SERT+/+ and SERT-/- rats. Results A clear reduction in the number of ejaculations was found in SERT-/- rats compared with SERT+/+ rats. As shown before, the combination of Atlas987 and paroxetine acutely reduced the number of ejaculations in wildtype rats. No effects of paroxetine and Atlas987 were found in SERT-/- rats. In addition, Atlas987 alone did not influence the number of ejaculations in both SERT+/+ and SERT-/- rats. This suggests that the 5-HT1A receptor involved with sexual behavior is desensitized in SERT-/- animals. Conclusions Enduro successfully inhibited sexual behavior in SERT+/+ rats, but had no effects on SERT-/- rats. Knocking out the serotonin transporter gene probably decreased the sensitivity to a 5-HT1A antagonist in sexual behavior. Conflicts of Interest All authors declare to have no conflicts of interest.

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