Drug‐Induced Sexual Dysfunction in Rats

Johnny S.W. Chan1, Marcel D. Waldinger2, Berend Olivier3, Ronald. S. Oosting1

1 Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands, 2 Department of Psychiatry and Neurosexology, Haga Hospital Leyenburg, The Hague, The Netherlands, 3 Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.34
DOI:  10.1002/0471142301.ns0934s53
Online Posting Date:  October, 2010
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This unit describes the testing of sexual behaviors of male Wistar rats. The described test enables the detection of stimulatory and inhibitory profiles of compounds. The test includes four training sessions to reach a stable sexual performance, followed by acute and/or chronic administration of drugs. The main quantifiable sexual behaviors are number of mounts (no vaginal penetration), intromissions (vaginal penetration), and ejaculations. By comparing the test compound to reference compound(s), sexual (side) effects can be determined. Curr. Protoc. Neurosci. 53:9.34.1‐9.34.11. © 2010 by John Wiley & Sons, Inc.

Keywords: sexual behavior; ejaculation; rats; SSRI; dysfunction

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Table of Contents

  • Introduction
  • Strategic Planning
  • Basic Protocol 1: Sexual Behavior in Rats
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1: Sexual Behavior in Rats

  • Adult Wistar male rats, 300 to 400 g
  • Adult Wistar female rats, 200 to 300 g
  • Rat food and water
  • Estradiol solution (for female rats; see recipe)
  • Paroxetine (test compound solutions; see recipe) as the reference compound (in pure form: Sigma‐Aldrich, cat. no. P9623; in tablet form: Paxil or generic brand from a pharmacy)
  • Observation cage (e.g., 60 × 30 × 40–cm with a Plexiglas front) with bedding material (e.g., can be self‐built or bought as an aquarium fish tank)
  • Scoring device with observing program or video recording equipment (e.g., Psion)
  • Workabout Pro with Noldus Pocket Observer software (Noldus)
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Literature Cited

Literature Cited
   Ågmo, A. and Ellingsen, E. 2003. Relevance of non‐human animal studies to the understanding of human sexuality. Scand. J. Psychol. 44:293‐301.
   Ahlenius, S., K. Larsson, K., and Svensson, L. 1980. Further evidence for an inhibitory role of central 5‐HT in male rat sexual behavior. Psychopharmacology 68:217‐220.
   Aversa, A., Bruzziches, R., Pili, M., and Spera, G. 2006. Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Curr. Pharm. Des. 12:3467‐3484.
   Balon, R. 2006. SSRI‐associated sexual dysfunction. Am. J. Psychiatry 163:1504‐1509.
   Chan, J.S., Olivier, B., de Jong, T.R., Snoeren, E.M., Kooijman, E., van Hasselt, F.N., Limpens, J.H., Kas, M.J., Waldinger, M.D., and Oosting, R.S. 2008, Translational research into sexual disorders: Pharmacology and genomics. Eur. J. Pharmacol. 585:426‐435.
   de Jong, T.R., Pattij, T., Veening, J.G., Dederen, P.J., Waldinger, M.D., Cools, A.R., and Olivier, B. 2005a. Effects of chronic paroxetine pretreatment on (+/−)‐8‐hydroxy‐2‐(di‐n‐propyl‐amino)tetralin induced c‐fos expression following sexual behavior. Neuroscience 134:1351‐1361.
   de Jong, T.R., Pattij, T., Veening, J.G., Waldinger, M.D., Cools, A.R., and Olivier, B. 2005b. Effects of chronic selective serotonin reuptake inhibitors on 8‐OH‐DPAT‐induced facilitation of ejaculation in rats: Comparison of fluvoxamine and paroxetine. Psychopharmacology 179:509‐515.
   Lorrain, D.S., Matuszewich, L., Friedman, R.D., and Hull, E.M. 1997. Extracellular serotonin in the lateral hypothalamic area is increased during the postejaculatory interval and impairs copulation in male rats. J. Neurosci. 17:9361‐9366.
   Marson, L. and McKenna, K.E. 1992. A role for 5‐hydroxytryptamine in descending inhibition of spinal sexual reflexes. Exp. Brain Res. 88:313‐320.
   Montgomery, S.A., Baldwin, D.S., and Riley, A. 2002. Antidepressant medications: A review of the evidence for drug‐induced sexual dysfunction. J. Affect. Disord. 69:119‐140.
   Mos, J., Mollet, I., Tolboom, J.T., Waldinger, M.D., and Olivier, B. 1999. A comparison of the effects of different serotonin reuptake blockers on sexual behaviour of the male rat. Eur. Neuropsychopharmacol. 9:123‐135.
   Olivier, B., Chan, J.S., Pattij, T., de Jong, T.R., Oosting, R.S., Veening, J.G., and Waldinger, M.D. 2006. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions? Int. J. Impot. Res. 18:S14‐S23.
   Pattij, T., de Jong, T.R., Uitterdijk, A., Waldinger, M.D., Veening, J.G., Cools, A.R., van der Graaf, P.H., and Olivier, B. 2005. Individual differences in male rat ejaculatory behaviour: Searching for models to study ejaculation disorders. Eur. J. Neurosci. 22:724‐734.
   Portfors, C.V. 2007. Types and functions of ultrasonic vocalizations in laboratory rats and mice. J. Am. Assoc. Lab. Anim. Sci. 46:28‐34.
   Rosen, R.C., Lane, R.M., and Menza, M. 1999. Effects of SSRIs on sexual function: a critical review. J. Clin. Psychopharmacol. 19:67‐85.
   Rosenzweig‐Lipson, S., Beyer, C.E., Hughes, Z.A., Khawaja, X., Rajarao, S.J., Malberg, J.E., Rahman, Z., Ring, R.H., and Schechter, L.E. 2007. Differentiating antidepressants of the future: Efficacy and safety. Pharmacol. Ther. 113:134‐153.
   Timmermans, P.J.A. 1978. Social Behavior in the Rat. Ph.D Thesis, University of Nijmegen.
   Vega Matuszcyk, J., Larsson, K., and Eriksson, E. 1998. The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. Pharmacol. Biochem. Behav. 60:527‐532.
   Waldinger, M.D., Hengeveld, M.W., Zwinderman, A.H., and Olivier, B. 1998. Effect of SSRI antidepressants on ejaculation: A double‐blind, randomized, placebo‐controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline. J. Clin. Psychopharmacol. 18:274‐281.
   Waldinger, M.D., Zwinderman, A.H., and Olivier, B. 2001a. Antidepressants and ejaculation: A double‐blind, randomized, placebo‐controlled, fixed‐dose study with paroxetine, sertraline, and nefazodone. J. Clin. Psychopharmacol. 21:293‐297.
   Waldinger, M.D., Zwinderman, A.H., and Olivier, B. 2001b. SSRIs and ejaculation: A double‐blind, randomized, fixed‐dose study with paroxetine and citalopram. J. Clin. Psychopharmacol. 21:556‐560.
   Waldinger, M.D., van De Plas, A., Pattij, T., van Oorschot, R., Coolen, L.M., Veening, J.G., and Olivier, B. 2002. The selective serotonin re‐uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment. Psychopharmacology 160:283‐289.
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