Abstract
Rationale
Sexual dysfunction is associated with antidepressant discontinuation. Therefore, there is a need for models that predict antidepressant-induced sexual dysfunction.
Objective
To develop a predictive method for evaluating antidepressant-induced sexual dysfunction.
Methods
Male Sprague–Dawley rats were allowed access to sexually receptive females during a single overnight mating session and then treated with antidepressants known to produce differing levels of sexual dysfunction in the clinic. Two to three weeks later, following either acute, subchronic (7-day), or chronic (14-day) antidepressant treatment, rats were observed for penile erections (PE) in the presence of sexually receptive females that were not accessible for contact but served as visual, auditory, and olfactory stimuli in the testing area.
Results
Chronic treatment of fluoxetine (10 mg/kg), desipramine (10 mg/kg), and bupropion (20 mg/kg) reduced the number of PE 71, 53, and 8%, respectively, relative to vehicle-treated rats. This rank order of the compounds’ propensity for reducing PE is comparable to the rank order of the compounds’ ability to produce sexual dysfunction during antidepressant treatment in the clinic. Additionally, drugs used to treat antidepressant-induced sexual dysfunction in the clinic, such as sildenafil, yohimbine, and dopamine agonists, were also effective in attenuating the deficits in the number of noncontact PE produced by chronic fluoxetine treatment.
Conclusions
Taken together, this model represents a novel approach for predicting antidepressant-induced sexual dysfunction in rats, which parallels the pattern of reports of sexual dysfunction in the clinic associated with different antidepressant treatments and the ability of adjunct treatment to reverse the sexual impairments produced by antidepressants.
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Abbreviations
- SSRI:
-
selective serotonin reuptake inhibitor
- mg:
-
milligram
- kg:
-
kilogram
- ANOVA:
-
analysis of variance
- TCA:
-
tricyclic antidepressants
- D/NRI:
-
dopamine/norepinephrine reuptake inhibitor
- PDE-5:
-
phosphodiesterase 5 inhibitor
- MED:
-
minimal effective dose
- 5-HT:
-
5-hydroxytryptophan
- s.c.:
-
subcutaneous
- i.p.:
-
intraperitoneal
- PE:
-
penile erection
References
Agmo A, Turi AL, Ellingsen E, Kaspersen H (2004) Preclinical models of sexual desire: conceptual and behavioral analyses. Pharmacol Biochem Behav 78:379–404
Ahn GJ, Kahg KK, Kim DS, Ahn BO, Kim WB, Kang SK, Lee BC, Hwang WS (2005) DA-8159 reverses selective serotonin inhibitor-induced erectile dysfunction in rats. Urology 65:202–207
American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DC
Angulo J, Bischoff E, Gabancho S, Cuevas P, Saenz de Tejada I (2003) Vardenafil reverses erectile dysfunction induced by paroxetine in rats. Int J Impot Res 15:90–93
Baldwin DS (2001) Depression and sexual dysfunction. Br Med Bull 57:81–99
Balon R (1993) Fluoxetine-induced sexual dysfunction and yohimbine. J Clin Psychiatry 54:161–162
Clayton AH, McGarvey EL, Abouesh AI, Pinkerton RC (2001) Substitution of an SSRI with bupropion sustained release following SSRI-induced sexual dysfunction. J Clin Psychiatry 62(3):185–190
Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, Bolden-Watson C, Bass KI, Donahue RMJ, Jamerson BD, Metz A (2002) Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 63:357–366
Coleman CC, King BR, Bolden-Watson C, Book MJ, Segraves RT, Richard N, Ascher J, Batey S, Jamerson B, Metz A (2001) A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Clin Ther 23(7):1040–1058
Croft H, Settle E Jr, Houser T, Batey SR, Donahue RM, Ascher JA (1999) A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther 21:643–658
Ferguson JM (2001) The effects of antidepressants on sexual functioning in depressed patients: a review. J Clin Psychiatry 62(Suppl 3):22–34
Frank JL, Hendricks SE, Olson CH (2000) Multiple ejaculations and chronic fluoxetine: effects on male rat copulatory behavior. Pharmacol Biochem Behav 66:337–342
Giuliano F, Rampin O (2004) Neural control of erection. Physiol Behav 83:189–201
Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM (2002) Antidepressant-induced sexual dysfunction. Ann Pharmacother 36:1577–1589
Harrison WM, Rabkin JG, Ehrhardt AA, Stewart JW, McGrath PJ, Ross D, Quitkin FM (1986) Effects of antidepressant medication on sexual function: A controlled study. J Clin Psychopharmacol 6:144–149
Jacobsen FM (1992) Fluoxetine-induced sexual dysfunction and an open trial of yohimbine. J Clin Psychiatry 53:119–122
Joly D, Sanger DJ (1986) The effects of fluoxetine and zimeldine on the behavior of olfactory bulbectomy in rats. Pharmacol Biochem Behav 24:199–204
Melis MR, Succu S, Mauri A, Argiolas A (1998) Nitric oxide production is increased in the paraventricular nucleus of the hypothalamus of male rats during non-contact penile erections and copulation. Eur J Neurosci 10:1968–1974
Michelson D, Kociban K, Tamura R, Morrison MF (2002) Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial. J Psychiatr Res 36:147–152
Modell JG, Katholi CR, Modell JD, DePalma RL (1997) Comparative sexual side effects of bupropion, fluoxetine, paroxetine, and sertraline. Clin Pharmacol Ther 61(4):476–487
Montgomery SA, Baldwin DS, Riley A (2002) Antidepressant medications: a review of the evidence for drug-induced sexual dysfunction. J Affect Disord 69:119–140
Morales A (2001) Yohimbine in erectile dysfunction: would an orphan drug ever be properly assessed? World J Urol 19:251–255
Mos J, Mollet I, Tolboom JTBM, Waldinger MD, Olivier B (1999) A comparison of the effects of different serotonin reuptake blockers on sexual behavior of the male rat. Eur Neuropsychopharmacol 9:123–135
Nurnberg HG (2001) Managing treatment-emergent sexual dysfunction associated with serotonergic antidepressants: before and after sildenafil. J Psychiatr Pract 7:92–108
Nurnberg HG, Hensley P (2003) Selective phosphodiesterase type-5 inhibitor treatment of serotonergic reuptake inhibitor antidepressant-associated sexual dysfunction. CNS Spectr 8:194–202
Nurnberg HG, Hensley PL, Lauriello J, Parker LM, Keith SJ (1999) Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Serv 50:1076–1078
Nurnberg HG, Hensley P, Gelenberg A, Fava M, Lauriello P, Paine S (2003) Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial. JAMA 289:56–64
Redolat R, Vidal J, Gomez MC, Carrasco MC (2005) Effects of acute bupropion administration on locomotor activity in adolescent and adult mice. Behav Pharmacol 16(1):59–62
Reneric J, Lucki I (1998) Antidepressant behavioral effects by dual inhibition of monoamine reuptake in the rat forced swimming test. Exp Clin Psychopharmacol 136:190–197
Roose SP (1999) Tolerability and patient compliance. J Clin Psychiatry 60(Suppl 17):14–17
Rothschild AJ (2000) New directions in the treatment of antidepressant-induced sexual dysfunction. Clin Ther 22(Suppl A):42–61
Sachs BD, Akasofu K, Citron JH, Daniels SB, Natoli JH (1994) Noncontact stimulation from estrous females evokes penile erection in rats. Physiol Behav 55:1073–1079
Shen WW, Urosevich Z, Clayton DO (1999) Sildenafil in the treatment of female sexual dysfunction induced by selective serotonin reuptake inhibitors. J Reprod Med 44:535–542
Sukoff Rizzo SJ, Schechter LE, Rosenzweig-Lipson S (2005) A novel approach for evaluating antidepressant-induced sexual dysfunction in rats. Soc Neurosci Abstr 559:4
Vega Matuszcyk J, Larrson K, Erikkson E (1998) The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in rats. Pharmacol Biochem Behav 60:527–532
Waldinger MD, van De Plas A, Pattij T, van Oorschot R, Coolen LM, Veening JG, Olivier B (2002) The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment. Psychopharmacology 160:283–289
West CHK, Weiss JM (1998) Effects of antidepressant drugs on rats bred for low activity in the swim test. Pharmacol Biochem Behav 61(1):67–79
Wilkinson JL, Bevins RA (2007) Bupropion hydrochloride produces conditioned hyperactivity in rats. Physiol Behav 90(5):790–796
Worthington JJ, Peters PM (2003) Treatment of antidepressant-induced sexual dysfunction. Drugs Today 39(11):887–896
Worthington JJ, Simon NM, Korbly NB, Perlis RH, Pollack MH (2002) Ropinirole for antidepressant-induced sexual dysfunction. Int Clin Psychopharmacol 17:307–310
Zajecka J (2001) Strategies for the treatment of antidepressant-related sexual dysfunction. J Clin Psychiatry 62(Suppl 3):35–43
Acknowledgement
The authors wish to thank Dr. Chad Beyer for critical review of this manuscript and Dr. Youping Huang for technical assistance.
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Sukoff Rizzo, S.J., Schechter, L.E. & Rosenzweig-Lipson, S. A novel approach for predicting antidepressant-induced sexual dysfunction in rats. Psychopharmacology 195, 459–467 (2008). https://doi.org/10.1007/s00213-007-0924-7
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DOI: https://doi.org/10.1007/s00213-007-0924-7