Flibanserin and 8-OH-DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair-bond quality.
BACKGROUND
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-HT(1A) agonist and 5-HT(2A) antagonist, shows promise as a treatment for HSDD.


OBJECTIVE
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.


METHODS
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.
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA. auberty@lacdr.leidenuniv.nl
Yves
Y
Aubert
Morgan L
ML
Gustison
Lindsey A
LA
Gardner
Michael A
MA
Bohl
Jason R
JR
Lange
Kelly A
KA
Allers
Bernd
B
Sommer
Nicole A
NA
Datson
David H
DH
Abbott
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002144:Callithrix; D005260:Female; D008297:Male; D023421:Models, Animal; D010152:Pair Bond; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D001562:Benzimidazoles; D018490:Serotonin Agents; D012701:Serotonin; C098107:flibanserin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin