BACKGROUND: Flibanserin, a novel serotonin (5-HT)(1A) agonist and 5-HT(2A) 
antagonist, has been shown to increase sexual desire and reduce distress in 
women with Hypoactive Sexual Desire Disorder (HSDD). In marmoset monkeys, 
flibanserin has demonstrated pro-social effects on male-female pairmates, while 
the classic 5-HT(1A) agonist 8-OH-DPAT suppresses female sexual behavior and 
increases aggressive interactions between pairmates. Activation of 5-HT(1A) and 
5-HT(2A) receptors is known to stimulate the hypothalamic-pituitary-adrenal 
(HPA) axis. This study aims to characterize the effects of repeated flibanserin 
and 8-OH-DPAT administration on the marmoset HPA axis and to elucidate endocrine 
correlates of altered marmoset pair behavior.
METHODS: Adrenocorticotropic hormone (ACTH) and cortisol were examined at 
baseline and during 5-HT(1A) agonist and restraint challenges in 8 female 
marmoset monkeys receiving daily flibanserin (15mg/kg) and an additional 8 
female marmosets receiving 8-OH-DPAT (0.1mg/kg) for 15-16weeks. Corresponding 
vehicle treatments were administered in a counterbalanced, within-subject 
design. All females were housed in stable male-female pairs. Treatment-induced 
changes in ACTH and cortisol levels were correlated with previously assessed 
marmoset pair behavior.
RESULTS: While morning basal cortisol levels and HPA responses to a 5-HT(1A) 
agonist challenge were not altered by chronic flibanserin or 8-OH-DPAT, both 
treatments increased the responsiveness of the marmoset HPA axis to restraint. 
Enhanced ACTH responses to restraint correlated with reduced sexual receptivity 
and increased aggression in 8-OH-DPAT-, but not in flibanserin-treated female 
marmosets.
CONCLUSIONS: Unaltered HPA responses to a 5-HT(1A) agonist challenge after 
chronic flibanserin and 8-OH-DPAT treatments indicate little or no 
de-sensitization of the HPA axis to repeated 5-HT(1A) manipulation. Chronic 
8-OH-DPAT, but not flibanserin, leads to aggravated ACTH responses to stress 
that may contribute to anti-sexual and anti-social behavior between 
8-OH-DPAT-treated females and their male pairmates. Despite similar flibanserin 
and 8-OH-DPAT induced ACTH responses to restraint stress, flibanserin-treated 
females show unchanged cortisol profiles. This is possibly due to flibanserin's 
regional selectivity in 5-HT(1A) activation and concurrent 5-HT(2A) inhibition. 
The contrasting restraint-related cortisol responses emulate contrasting 
behavioral phenotypes of diminished pair-bond of 8-OH-DPAT-treated females 
compared to the more affiliative pair-bond of flibanserin-treated females.