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Flibanserin and 8-OH-DPAT Implicate Serotonin in Association between Female Marmoset Monkey Sexual Behavior and Changes in Pair-Bond Quality

Authors

  • Yves Aubert MS,

    Corresponding author
    1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
    2. Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Centre, Leiden, The Netherlands
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  • Morgan L. Gustison MS,

    1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
    2. Department of Psychology, University of Michigan, Ann Arbor, MI, USA
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  • Lindsey A. Gardner BS,

    1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
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  • Michael A. Bohl BA,

    1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
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  • Jason R. Lange BS,

    1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
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  • Kelly A. Allers PhD,

    1. Department of CNS Diseases, Boehringer Ingelheim, Biberach, Germany
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  • Bernd Sommer PhD,

    1. Department of CNS Diseases, Boehringer Ingelheim, Biberach, Germany
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  • Nicole A. Datson PhD,

    1. Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Centre, Leiden, The Netherlands
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  • David H. Abbott PhD

    1. Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA
    2. Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI, USA
    3. Endocrinology-Reproductive Physiology Training Program, University of Wisconsin-Madison, Madison, WI, USA
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Yves Aubert, MS, Medical Pharmacology, LACDR, Leiden University Medical Centre, Einsteinweg 55, 2333 CC Leiden, the Netherlands. Tel: +31715276301; Fax: +31715274715; E-mail: auberty@lacdr.leidenuniv.nl

ABSTRACT

Introduction.  Psychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5-HT). Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, shows promise as a treatment for HSDD.

Aim.  To test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8-OH-DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans.

Methods.  Sexual and social behavior were examined in eight female marmoset monkeys receiving daily flibanserin (15 mg/kg), 8-OH-DPAT (0.1 mg/kg), or corresponding vehicle for 15–16 weeks in a counterbalanced, within-subject design, while housed in long-term, stable male–female pairs.

Main Outcome Measures.  Marmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5–6 of daily flibanserin, 8-OH-DPAT or vehicle treatment. 24-hour pharmacokinetic profiles of the drugs and their metabolites, as well as drug-induced acute symptoms of the 5-HT behavioral syndrome were also assessed.

Results.  Two-way analysis of variance reveals that flibanserin-treated females attract more male sexual interest (P = 0.020) and trigger increased grooming (P = 0.001) between partners. In contrast, 8-OH-DPAT-treated females show increased rejection of male sexual advances (P = 0.024), a tendency for decreased male sexual interest (P = 0.080), and increased aggression with their male pairmates (P = 0.049).

Conclusions.  While 8-OH-DPAT-treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin-treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro-affiliation attributes may underlie flibanserin's effectiveness in treating HSDD in women. Aubert Y, Gustison ML, Gardner LA, Bohl MA, Lange JR, Allers KA, Sommer B, Datson NA, and Abbott DH. Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality. J Sex Med 2012;9:694–707.

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