medigraphic.com
Academia Mexicana de Neurología, A.C.

2015, Number 2

<< Back Next >>

Rev Mex Neuroci 2015; 16 (2)

The multiple partner choice arena: An innovative model for studying rapid ejaculation in rats

Olayo-Lortia J, Ferreira-Nuño A, Morales-Otal A

Language: Spanish
References: 38
Page: 16-26
PDF size: 217.00 Kb.


ABSTRACT

Introduction: Premature ejaculation in humans is one of the most common sexual dysfunctions of global population. The knowledge of the neurobiology of this dysfunction through animal models is important because these models can propose better therapeutic options to treat this dysfunction. Our research group has developed an innovative model, the Multiple Parther Choice Arena, which have shown that male rats ejaculate faster so that this model could be useful in evaluating different drugs.
Objectives: To evaluate the response of our model to the drug currently used in the clinic, dapoxetine, at dose is indicated as a treatment for premature ejaculation in humans.
Methods: Two male sexual behavior tests were performed in the multiple partner choice arena (MPCA) to two groups of rats were treated with vehicle and 30 mg / kg of dapoxetine respectively.
Results: The males rats treated with dapoxetine, significantly increased the number of mounts and number of intrusions that require to ejaculate as well as increased intromission latency and intromission and ejaculation latency in the MPCA.
Conclusion: Males who are treated with dapoxetine at ASMP stop behaving such as rapid ejaculators.


REFERENCES

  1. McMahon CG, Jannini E, Waldinger M, Rowland D. Standard operating procedures in the disorders of orgasm and ejaculation. J Sex Med 2013; 1: 204-229.

  2. Graziottin A, Althof S. What does premature ejaculation mean to the man, the woman, and the couple? J Sex Med 2011; (Suppl 4), 304-309.

  3. Waldinger M.D, Olivier, B. Selective serotonin reuptake inhibitor-induced sexual dysfunction: clinical and research considerations. Int Clin Psychopharmacol 1998; (Suppl 6): S27-33.

  4. Olivier B, Chan JS, Pattij T, de Jong TR, Oosting RS, Veening JG, Waldinger MD. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions? Int J Impot Res 2006; (Suppl 1): S14-23.

  5. Hull EM, Dominguez, J. Sexual behavior in male rodents. Horm Behav 2007; 1: 45-55.

  6. Pattij T, Olivier B, Waldinger, MD. Animal models of ejaculatory behavior. Curr Pharm Des 2005; 31: 4069-4077.

  7. Mos J, Mollet I, Tolboom JT, Waldinger MD, Olivier B. A comparison of the effects of different serotonin reuptake blockers on sexual behaviour of the male rat. Eur Neuropsychopharmacol 1999; 1-2: 123-135.

  8. Vega-Matuszcyk J, Larsson K, Eriksson E. The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. Pharmacol Biochem Behav 1998; 2: 527-532.

  9. Hueletl-Soto ME, Carro-Juárez M, Rodríguez-Manzo G. Fluoxetine chronic treatment inhibits male rat sexual behavior by affecting both copulatory behavior and the genital motor pattern of ejaculation. J Sex Med 2012; 4: 1015-1026.

  10. Morales-Otal A, Ferreira-Nuño A, Velázquez-Moctezuma J. Monoaminergic and cholinergic stimulation of masculine sexual behavior in neonatally demasculinized male rats. Pharmacol Res 2002; 1: 61-66.

  11. Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, et al Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav 1981; 5: 785-792.

  12. Hillegaart V, Ahlenius S. Facilitation and inhibition of male rat ejaculatory behaviour by the respective 5-HT1A and 5-HT1B receptor agonists 8-OH-DPAT and anpirtoline, as evidenced by use of the corresponding new and selective receptor antagonists NAD-299 and NAS-181. Br J Pharmacol 1998; 8: 1733-1743.

  13. Ahlenius S, Larsson K. Evidence for an involvement of 5-HT1B receptors in the inhibition of male rat ejaculatory behavior produced by 5-HTP. Psychopharmacology (Berl) 1998; 4: 374-382.

  14. Fernández-Guasti A, Escalante AL, Ahlenius S, Hillegaart V, Larsson K. Stimulation of 5-HT1A and 5-HT1B receptors in brain regions and its effects on male rat sexual behaviour. Eur J Pharmacol 1992; 2: 121-129.

  15. Ferreira-Nuño A, Fernández-Soto C, Olayo-Lortia J, Ramirez-Carreto R, Paredes RG, Velázquez- Moctezuma J, Morales-Otal A. Copulatory pattern of male rats in a multiple partner choice arena. J Sex Med 2010; 12: 3845-3856.

  16. Olayo-Lortia, J., Ferreira-Nuño A, Velázquez-Moctezuma J, Morales-Otal A. Further definition on the multiple partner choice arena: a potential animal model for the study of premature ejaculation. J Sex Med 2014; 10: 2428 – 2438.

  17. Ferreira-Nuño A, Morales-Otal A, Paredes, RG, Velázquez-Moctezuma J. Sexual behavior of female rats in a multiple-partner preference test. Horm Behav 2005; 3: 290-296.

  18. Waldinger MD, Schweitzer DH, Olivier B. Dapoxetine treatment of premature ejaculation. Lancet 2006; 9550: 1869-1870.

  19. McMahon, CG. Dapoxetine: a new option in the medical management of premature ejaculation. Ther Adv Urol 2012; 4: 233-251

  20. Fernández-Guasti A, Rodríguez-Manzo G. Pharmacological and physiological aspects of sexual exhaustion in male rats. Scand J Psychol 2003; 44: 257–263

  21. Ferreira-Nuño A, Overstreet DH, Morales-Otal A, Velázquez-Moctezuma J. Masculine sexual behavior features in the Flinders sensitive and resistant line rats. Behav Brain Res 2002; 128: 113- 119

  22. McMahon, CG. Dapoxetine for premature ejaculation. Expert Opin Pharmacother 2010; 11: 1741- 1752.

  23. Feige AM, Pinsky MR, Hellstrom WJ. Dapoxetine for premature ejaculation. Clin Pharmacol Ther 2011; 8: 125-128.

  24. Gengo PJ, View M, Giuliano F, McKenna KE, Chester A, Lovenberg T et al. Monoaminergic transporter binding and inhibition profile of dapoxetine, a medication for the treatment of premature ejaculation. J Urol 2005; 4: 239-239.

  25. Livni E, Satterlee W, Robey RL, Alt CA, Van Meter EE, Babich JW et al. Synthesis of [11C] dapoxetine. HCl, a serotonin re-uptake inhibitor: biodistribution in rat and preliminary PET imaging int he monkey. Nucl Med Biol 1994; 21: 669-675.

  26. Jeong I, Kim S, Yoon S, Hahn S. Block of cloned Kv4.3 potassium channels by dapttoxetine. Neuropharmacology 2012; 62: 2261-2266.

  27. Clément P, Laurin M, Compagnie S, Facchinetti P, Bernabé J, Alexandre L et al. Effect of Dapoxetine on Ejaculatory Performance and Related Brain Neuronal Activity in Rapid Ejaculator Rats. J Sex Med 2012; 9: 2562-2573

  28. Giuliano F, Bernabé J, Gengo P, Alexandre L, Clément P. Effect of acute dapoxetine administration on the pudendal motoneuron reflex in anesthetized rats: comparison with paroxetine. J Urol 2007; 177: 386-389

  29. Giuliano F. Premature ejaculation: definition and drug treatment. Drugs 2007; 67: 1629-1630.

  30. Waldinger MD. The neurobiological approach to premature ejaculation. J Urol 2002; 168: 2359- 2367.

  31. Olivier B, Chan JS, Snoeren EM, Olivier JD, Veening JG, Vinkers CH et al.. Differences in sexual behaviour in male and female rodents: role of serotonin. Curr Top Behav Neurosci 2011; 8: 15-36.

  32. Morales A. Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment - topical versus systemic. Can Urol Assoc J 2012; 5: 380 - 385.

  33. Olivier B. Serotonin: A never-ending story. Eur J Pharmacol. 2014 doi: 10.1016/j. ejphar.2014.10.031.

  34. de Jong TR, Veening JG, Waldinger MD, Cools AR, Olivier B. Serotonin and the neurobiology of the ejaculatory threshold. Neurosci Biobehav Rev 2006; 7: 893-907.

  35. Pryor JL, Althof SE, Steidle C, Rosen RC, Hellstrom WJ, Shabsigh R et al. Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials. Lancet 2006; 9539: 929-939.

  36. Buvat J, Tesfaye F, Rothman M, Rivas DA, Giuliano F. Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries. Eur Urol 2009; 4: 957-967.

  37. Porst HH, McMahon CG, Althof SE, Sharlip I, Bull S, Aquilina JW. Rivas DA. Baseline characteristics and treatment outcomes for men with acquired or lifelong premature ejaculation with mild or no erectile dysfunction: integrated analyses of two phase 3 dapoxetine trials. J Sex Med 2010; 6: 2231- 2242.

  38. McMahon CG, Althof SE, Kaufman JM, Buvat J, Levine SB, Aquilina JW et al. Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials. J Sex Med 2011; 2: 524-539




2020     |     www.medigraphic.com