title: Flibanserin-Stimulated Partner Grooming Reflects Brain Metabolism Changes in Female Marmosets.
abstract: BACKGROUND
  Female sexual interest and arousal disorder is personally distressing for women. To better understand the mechanism of the candidate therapeutic, flibanserin, we determined its effects on an index of brain glucose metabolism.
  
  
  OBJECTIVE
  We hypothesized that chronic treatment with flibanserin would alter metabolism in brain regions associated with serotonergic function and female sexual behavior.
  
  
  METHODS
  In a crossover design, eight adult female common marmosets (Calithrix jacchus) received daily flibanserin or vehicle. After 7-12 weeks of treatment, the glucose metabolism radiotracer [(18) F]fluorodeoxyglucose (FDG) was administered to each female immediately prior to 30 minutes of interaction with her male pairmate, after which females were anesthetized and imaged by positron emission tomography. Whole-brain normalized images were analyzed with anatomically defined regions of interest. Whole-brain voxelwise mapping was used to explore treatment effects. Correlations were examined between alterations in metabolism and pairmate social grooming.
  
  
  METHODS
  Changes in metabolism associated with flibanserin were determined for dorsal raphe, medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus, and field cornu ammonis 1 (CA1) of the hippocampus.
  
  
  RESULTS
  In response to chronic flibanserin, metabolism in mPOA declined, and this reduction correlated with increases in pairmate grooming. A cluster of voxels in frontal cortico-limbic regions exhibited reduced metabolism in response to flibanserin and overlapped with a voxel cluster in which reductions in metabolism correlated with increases in pairmate grooming. Finally, reductions in mPOA metabolism correlated with increases in metabolism in a cluster of voxels in somatosensory cortex.
  
  
  CONCLUSIONS
  Taken together, these results suggest that flibanserin-induced reductions in female mPOA neural activity increase intimate affiliative behavior with male pairmates.
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Alexander K
authors.identifier: http://orcid.org/0000-0002-2035-9331
authors.initials: AK
authors.lastname: Converse
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.|Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
authors.forename: Yves
authors.initials: Y
authors.lastname: Aubert
authors.affiliation: Department of CNS Diseases, Boehringer Ingelheim, Biberach, Germany.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Allers
authors.affiliation: Department of CNS Diseases, Boehringer Ingelheim, Biberach, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Sommer
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.|Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI, USA.|Endocrinology-Reproductive Physiology Training Program, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Abbott
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001931:Brain Mapping; D002144:Callithrix; D005260:Female; D006120:Grooming / Q000187:drug effects*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D023421:Models, Animal; D010152:Pair Bond; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000473:pathology*; D018490:Serotonin Agents / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D018490:Serotonin Agents; C098107:flibanserin
keywords: Brain; Female Sexual Behavior; Flibanserin; Glucose Metabolism; Marmoset; Positron Emission Tomography