Serotonin Transporter Null Mutation and Sexual Behavior in Female Rats: 5-HT1A Receptor Desensitization

Authors

  • Eelke Snoeren MSc,

    Corresponding author
    1. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands;
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  • Johnny Chan BSc,

    1. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands;
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  • Astrid Bovens BSc,

    1. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands;
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  • Edwin Cuppen PhD,

    1. Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands;
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  • Marcel Waldinger MD, PhD,

    1. Department of Psychopharmacology, 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. Department of Psychopharmacology, 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 Oosting PhD

    1. Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands;
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Eelke Snoeren, MSc, Department of Psychopharmacology, Utrecht University, Sorbonnelaan 16, Utrecht 3584CA, the Netherlands. Tel: 003130-2537383; Fax: 003130-2537900; E-mail: e.m.s.snoeren@uu.nl

ABSTRACT

Introduction.  Serotonin plays a key role in sexual behavior. In serotonin transporter (SERT) knockout rats (−/−), basal extracellular 5-HT levels are considerably increased, indicating a serotonergic disturbance. Heterozygous SERT(+/−) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SERT promoter (5-HTTLPR) polymorphism.

Aim.  In the present study, we used both homozygote and heterozygote SERT knockout and wild-type rats (+/+) to study the putative role of the SERT in female sexual behavior.

Methods.  Female rats were brought into estrous by hormonal injections before a paced mating sex test. The effects of the 5-HT1A/5-HT7 receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (±8-OH-DPAT) (0.03–1 mg/kg s.c.) and the 5-HT1A receptor antagonist WAY-100635 (0.1–1–mg/kg i.p.) on sexual behaviors of the females were tested separately and in a selected combination of both in all three genotypes.

Main Outcome Measures.  Proceptive (darting and hopping) and receptive (lordosis) behaviors were quantified.

Results.  Basal proceptive and receptive sexual activities were not different between SERT+/+, +/− and −/− female rats. The dose–effect curve after ±8-OH-DPAT for these activities was clearly shifted to the right in SERT−/− animals compared to other genotypes. WAY-100635 alone had no effect on sexual behavior in any genotype, but was able to antagonize the ±8-OH-DPAT-induced decrease in sexual activities indicating the involvement of the 5-HT1A receptor.

Conclusions.  The absence (−/−) or reduced (+/−) expression of SERT does not affect basal sexual activity in female rats in a paced mating situation. The data indicate a desensitized 5-HT1A receptor in the SERT−/−, but not in the SERT+/− females. Under normal basal conditions, desensitized 5-HT1A receptors apparently do not play a role in female sexual behavior of the SERT−/−. However, upon activation of the 5-HT1A receptor in “normal” females (SERT+/+ and SERT+/−), a hyposexual behavior is induced. Snoeren E, Chan J, Bovens A, Cuppen E, Waldinger M, Olivier B, and Oosting R. Serotonin transporter null mutation and sexual behavior in female rats: 5-HT1A receptor desensitization. J Sex Med 2010;7:2424–2434.

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