Chronic systemic administration of serotonergic ligands flibanserin and 8-OH-DPAT enhance HPA axis responses to restraint in female marmosets

Unaltered HPA responses to a 5-HT1A agonist challenge after chronic flibanserin and 8-OH-DPAT treatments indicate little or no de-sensitization of the HPA axis to repeated 5-HT1A 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-HT1A activation and concurrent 5-HT2A 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.