Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Effects of bupropion on the ejaculatory response of male rats

International Journal of Impotence Research volume 26, pages 205–212 (2014)Cite this article

Subjects

Abstract

Chronic antidepressant treatment is associated with sexual side effects, particularly affecting the ejaculatory response. Bupropion (BP), an antidepressant inhibiting dopamine/noradrenaline reuptake, seems to have a low impact upon male sexual function. Ejaculation is regulated both at the brain and spinal cord by the spinal generator for ejaculation (SGE). We investigated the effects of chronic BP treatment on ejaculatory behavior and on SGE functioning. Sexually experienced male rats were intraperitoneally (i.p.) injected with BP (7.5 or 15 mg kg−1) during 14 days and tested for sexual behavior on days 1, 7 and 14 of treatment; these same males were used to evaluate the functioning of the SGE by recording the genital motor pattern for ejaculation (GMPE). Acute and chronic BP administration did not importantly modify copulatory behavior of male rats. Chronic treatment with the low dose of BP produced deficits in the functioning of the SGE that were restored by activation of the SGE through afferent stimulation. Conversely, chronic treatment with the high-dose of BP disrupted the functioning of the SGE, as the deficits were not compensated by activating the SGE through sensory stimulation. It is concluded that chronic BP at high doses alters the functioning of the SGE.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 4
Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Montgomery SA, Baldwin DS, Riley A . Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. J Affect Disord 2002; 69: 119–140.

    Article  CAS  Google Scholar 

  2. Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, Bolden-Watson C et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002; 63: 357–366.

    Article  Google Scholar 

  3. Clayton AH, Montejo AL . Major depressive disorder, antidepressants, and sexual dysfunction. J Clin Psychiatry 2006; 67: 33–37.

    Google Scholar 

  4. Ferris RM, Cooper BR . Mechanism of antidepressant activity of bupropion. J Clin Psychiatry 1993; 11: 2–14.

    Google Scholar 

  5. Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S . A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry 2004; 6: 159–166.

    Article  Google Scholar 

  6. Baldwin DS . Sexual dysfunction associated with antidepressant drugs. Expert Opin Drug Saf 2004; 3: 457–470.

    Article  CAS  Google Scholar 

  7. Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM . Antidepressant-induced sexual dysfunction. Ann Pharmacother 2002; 36: 1577–1589.

    Article  CAS  Google Scholar 

  8. Chan JS, Olivier B, de Jong TR, Snoeren EM, Kooijman E, Van Hasselt FN et al. Translational research into sexual disorders: pharmacology and genomics. Eur J Pharmacol 2008; 585: 426–435.

    Article  CAS  Google Scholar 

  9. Sukoff-Rizzo SI, Schechter LE, Rosenzweig-Lipsson S . A novel approach for predicting antidepressant-induced sexual dysfunction in rat. Psychopharmacology 2008; 195: 459–467.

    Article  CAS  Google Scholar 

  10. Montejo-González AL, Llorca G, Izquierdo JA, Ledesma A, Bousoño M, Calcedo A et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther 1997; 23: 176–194.

    Article  Google Scholar 

  11. Demyttenaere K, Huygens R . Painful ejaculation and urinary hesitancy in association with antidepressant therapy: relief with tamsulosin. Eur Neuropsychopharmacol 2002; 12: 337–341.

    Article  CAS  Google Scholar 

  12. De Leo D, Magni G . Sexual side effects of antidepressant drugs. Psychosomatics 1983; 24: 1076–1082.

    Article  CAS  Google Scholar 

  13. Schwarcz G . Case report of inhibition.of ejaculation and retrograde ejaculation as side effects of amoxapine. Am J Psychiatry 1982; 139: 233–234.

    Article  CAS  Google Scholar 

  14. Peeters M, Giuliano F . Central neurophysiology and dopaminergic control of ejaculation. Neurosci Biobehav Rev 2008; 32: 438–453.

    Article  CAS  Google Scholar 

  15. Carro-Juárez M, Cruz SL, Rodríguez-Manzo G . Evidence for the involvement of a spinal pattern generator in the control of the genital motor pattern of ejaculation. Brain Res 2003; 975: 222–228.

    Article  Google Scholar 

  16. Carro-Juárez M, Rodríguez-Manzo G . The spinal pattern generator for ejaculation. Brain Res Rev 2008; 58: 106–120.

    Article  Google Scholar 

  17. Truitt WA, Coolen LM . Identification of a potential ejaculation generator in the spinal cord. Science 2002; 297: 1566–1569.

    Article  CAS  Google Scholar 

  18. Coolen LM, Allard J, Truitt WA, McKenna KE . Central control of ejaculation. Physiol Behav 2004; 83: 203–215.

    Article  CAS  Google Scholar 

  19. Xu C, Giuliano F, Yaici ED, Conrath M, Trassard O, Benoit G et al. Identification of lumbar spinal neurons controlling simultaneously the prostate and the bulbospongiosus muscles in the rat. Neuroscience 2006; 138: 561–573.

    Article  CAS  Google Scholar 

  20. Borgdorff AJ, Bernabé J, Denys P, Alexandre L, Giuliano F . Ejaculation elicited by microstimulation of lumbar spinothalamic neurons. Eur Urol 2008; 54: 449–456.

    Article  Google Scholar 

  21. Carro-Juárez M, Rodríguez-Manzo G . Sensory and motor aspects of the coital reflex in the spinal male rat. Behav Brain Res 2000; 108: 97–103.

    Article  Google Scholar 

  22. Rénéric JP, Lucki I . Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test. Psychopharmacology 1998; 136: 190–197.

    Article  Google Scholar 

  23. Nielsen JA, Shannon NJ, Bero L, Moore KE . Effects of acute and chronic bupropion on locomotor activity and dopaminergic neurons. Pharmacol Biochem Behav 1986; 24: 795–799.

    Article  CAS  Google Scholar 

  24. Suckow RF, Smith TM, Perumal AS, Cooper TB . Pharmaco-kinetics of bupropion and metabolites in plasma and brain of rats, mice, and guinea pigs. Drug Metab Dispos 1986; 14: 692–697.

    CAS  PubMed  Google Scholar 

  25. Arias HR, Santamaría A, Ali S . Pharmacological and neurotoxicological actions mediated by bupropion and diethylpropion. Int Rev Neurobiol 2009; 88: 223–255.

    Article  CAS  Google Scholar 

  26. Adachi H, Sato Y, Kato R, Hisasue S, Suzuki K, Masumori N et al. Direct evidence of facilitative actions of dopamine in the medial preoptic area on reflexive and noncontact erections in male rats. J Urol 2003; 169: 386–389.

    Article  CAS  Google Scholar 

  27. Hull EM, Rodríguez-Manzo G . Male sexual behavior. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT (eds) Hormones, Brain and Behavior 2nd edn vol. 1. Academic Press/Elsevier: San Diego, 2009 pp 5–65.

    Chapter  Google Scholar 

  28. Carro-Juárez M, Rodríguez-Manzo G . α-Adrenergic agents modulate the activity of the spinal pattern generator for ejaculation. Int J Impot Res 2006; 18: 32–38.

    Article  Google Scholar 

  29. Watcho P, Carro-Juárez M . Evaluation of the excopula ejaculatory potentials of Bersama engleriana in spinal male rats. Asian J Androl 2009; 11: 533–539.

    Article  Google Scholar 

  30. Benelli A, Zanoli P, Bertolini A . Effect of clenbuterol on sexual behavior in male rats. Physiol Behav 1990; 47: 373–376.

    Article  CAS  Google Scholar 

  31. Meisel R, Sachs B . The physiology of male sexual behaviour. In: Knobil Neill J (ed) The Physiology of Reproduction. Raven: New York, USA, 1994 pp 3–105.

    Google Scholar 

  32. Schweitzer I, Maguire K, Ng Ch . Sexual side-effects of contemporary antidepressants: review. Aust NZ J Psychiatry 2009; 43: 795–808.

    Article  Google Scholar 

  33. Wilkinson JL, Bevins RA . Bupropion hydrochloride produces conditioned hyperactivity in rats. Physiol Behav 2007; 90: 790–796.

    Article  CAS  Google Scholar 

  34. Santamaría A, Arias HR . Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats. Behav Brain Res 2010; 211: 132–139.

    Article  Google Scholar 

  35. Nomikos GG, Damsma G, Wenkstern D, Fibiger HC . Acute effects of bupropion on extracellular dopamine concentrations in rat striatum and nucleus accumbens studied by in vivo microdyalisis. Neuropsychopharmacology 1989; 2: 273–279.

    Article  CAS  Google Scholar 

  36. Sidhpura N, Redfern P, Rowley H, Heal D, Wonnacott S . Comparison of the effects of bupropion and nicotine on locomotor activation and dopamine release in vivo. Biochem Pharmacol 2007; 74: 1292–1298.

    Article  CAS  Google Scholar 

  37. Carro-Juárez M, Rodríguez-Manzo G . Role of genital sensory information in the control of the functioning of the spinal generator for ejaculation. Int J Impot Res 2005; 17: 114–120.

    Article  Google Scholar 

  38. Stafford AS, Coote HJ . Activation of D2-like receptors induces sympathetic climactic-like response in male and female anaesthetized rats. Br J Pharmacol 2006; 148: 510–516.

    Article  CAS  Google Scholar 

  39. Clement P, Bernabe J, Kia HK, Alexandre L, Giuliano F . D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino) tetralin in rats. J Pharmacol Exp Ther 2006; 316: 830–834.

    Article  CAS  Google Scholar 

  40. Gandolfi O, Barbaccia ML, Chuang DM, Costa E . Daily bupropion injections for 3 weeks attenuate the NE stimulation of adenylate cyclase and the number of beta-adrenergic recognition sites in rat frontal cortex. Neuropharmacology 1983; 22: 927–929.

    Article  CAS  Google Scholar 

  41. Hueletl-Soto ME, Carro-Juárez M, Rodríguez-Manzo G . DMI-induced sexual effects in male rats: analysis of DMI’s acute and chronic actions on copulatory behavior and on the genital motor pattern of ejaculation. Pharmacol Biochem Behav 2010; 94: 423–430.

    Article  CAS  Google Scholar 

  42. 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; 9: 1015–1026.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Mrs Ángeles Ceja for technical assistance and animal care. The data here presented were part of the PhD dissertation of María Eugenia Hueletl-Soto who received a fellowship from the Conacyt (no. 162252).

Author information

Authors and Affiliations

  1. Laboratorio de Comportamiento Reproductivo, Escuela de Medicina Veterinaria y Zootecnia, Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico

    M E Hueletl-Soto & M Carro-Juárez

  2. Departamento de Farmacobiología, CINVESTAV, IPN-Sede Sur, México City, Mexico

    M E Hueletl-Soto & G Rodríguez-Manzo

Authors
  1. M E Hueletl-Soto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Carro-Juárez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Rodríguez-Manzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G Rodríguez-Manzo.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hueletl-Soto, M., Carro-Juárez, M. & Rodríguez-Manzo, G. Effects of bupropion on the ejaculatory response of male rats. Int J Impot Res 26, 205–212 (2014). https://doi.org/10.1038/ijir.2014.12

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijir.2014.12

Search

Advanced search

Quick links