Chronic Paroxetine Treatment Does Not Affect Sexual Behavior in Hormonally Sub-primed Female Rats Despite 5-HT1A Receptor Desensitization

Authors

  • Eelke M.S. Snoeren PhD,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands
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  • Louise K. Refsgaard BSc,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands
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  • Marcel D. Waldinger MD, PhD,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands
    2. Department of Psychiatry and Neurosexuology, Haga Hospital Leyenburg, The Hague, the Netherlands
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  • Berend Olivier PhD,

    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands
    2. Yale University School of Medicine, New Haven, CT, USA
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  • Ronald S. Oosting PhD

    Corresponding author
    1. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, the Netherlands
      Ronald S. Oosting, PhD, Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, 3584CA, Utrecht, the Netherlands. Tel: +31 30 253 3730; Fax: +31 30 253 7900; E-mail: r.s.oosting@uu.nl
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Ronald S. Oosting, PhD, Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, 3584CA, Utrecht, the Netherlands. Tel: +31 30 253 3730; Fax: +31 30 253 7900; E-mail: r.s.oosting@uu.nl

ABSTRACT

Introduction.  Selective serotonin reuptake inhibitors (SSRIs) cause sexual dysfunctions in humans. However, because SSRIs are used to treat depression, it is unclear whether the problems are caused by the drug, by the depression itself, or an interaction between both.

Aim.  The present study investigated the effects of chronic paroxetine treatment on sexual behavior in female rats. Furthermore, we tested whether 5-hydroxytryptamine (5-HT)1A receptors were desensitized in these females.

Methods.  Ovariectomized female rats, either sub-primed with estradiol or fully primed with estradiol and progesterone, were tested in a paced mating test. Proceptive (darting and hopping), receptive (lordosis), and paced mating-related (percentages of exits and contact-return latencies) behaviors were quantified during the course of 56 days of chronic paroxetine treatment (10 mg/kg and 20 mg/kg per day). The 5-HT1A/5-HT7 receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide ((±)8-OH-DPAT) alone and in combination with the selective 5-HT1A receptor antagonist WAY-100635 was administered to study putative 5-HT1A desensitization in the same females.

Main Outcome Measures.  Proceptive, receptive, and paced mating behaviors were quantified.

Results.  Acute and chronic paroxetine treatment did not change proceptive and receptive behaviors in both sub-primed and fully primed female rats. In all groups, (±)8-OH-DPAT showed a clear dose-dependent inhibition of sexual behaviors in vehicle-treated females and a right-shifted dose–response effect in the paroxetine-treated rats. WAY-100635 attenuated the inhibiting effect of the 5-HT1A receptor agonist in all females. These data suggest 5-HT1A receptor desensitization after chronic paroxetine treatment.

Conclusions.  Chronic paroxetine treatment does not cause sexual side effects in sub- or fully hormonally primed female rats. Furthermore, chronic treatment causes adaptive changes in the serotonin system such as desensitization of 5-HT1A receptors, which may counteract the inhibiting effects of increased extracellular serotonin levels in the chronic paroxetine-treated rats. Snoeren EMS, Refsgaard LK, Waldinger MD, Olivier B, and Oosting RS. Chronic paroxetine treatment does not affect sexual behavior in hormonally sub-primed female rats despite 5-HT1A receptor desensitization. J Sex Med 2011;8:976–988.

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