title: Brain region-specific transcriptomic markers of serotonin-1A receptor agonist action mediating sexual rejection and aggression in female marmoset monkeys.
abstract: BACKGROUND
  In a marmoset model of hypoactive female sexual function, we have shown that repeated administration of the serotonin (5-HT)-1A agonist R-(+)-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) inhibits sexual receptivity in female marmoset monkeys and increases aggression toward the male pairmate.
  
  
  OBJECTIVE
  The aims of this study are to investigate gene expression changes induced by 8-OH-DPAT in laser-microdissected brain areas that regulate female sexual function and to identify genes, functional gene classes, and pathways associated with 8-OH-DPAT-mediated inhibition of female sexual receptivity.
  
  
  METHODS
  Gene expression was measured in the medial prefrontal cortex (mPFC), medial preoptic area (mPOA), cornu ammonis-1 (CA1) area of the hippocampus (CA1), and dorsal raphé nucleus (DRN) of four 8-OH-DPAT-treated (0.1 mg/kg; daily administration for 16 weeks) and four vehicle-treated female marmosets using a marmoset-specific microarray (European Marmoset Microarray [EUMAMA]) and validated by real-time quantitative polymerase chain reaction (RTqPCR). Enriched functional gene classes were determined. In a parallel candidate gene approach, the expression of serotonergic candidate genes, i.e., the 5-HT1A, 5-HT2A, and 5-HT7 receptors and the 5-HT transporter (5-HTT), was measured by RTqPCR.
  
  
  METHODS
  The main outcome is the differential expression of genes between 8-OH-DPAT- and vehicle-treated marmosets.
  
  
  RESULTS
  8-OH-DPAT affected the gene classes important to neural development (mPFC, mPOA, and DRN), neurotransmission (mPOA), energy production (mPFC and mPOA), learning and memory (CA1), and intracellular signal transduction (DRN). Oxytocin (OXT) in the mPOA and 5-HTT in the DRN were strongly increased by 8-OH-DPAT. 5-HT1A tended to increase in the mPFC, while 5-HT7 was decreased in the CA1.
  
  
  CONCLUSIONS
  Brain region-specific alterations of gene expression regulating neural circuitries, energy demands, and learning processes are associated with 8-OH-DPAT-induced decrease in female sexual receptivity and increase in pairmate aggression. The role of OXT in the serotonergic regulation of female sexual behavior and partner interactions warrants attention in future studies.
authors.affiliation: Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden, The Netherlands. yvesaubert@gmail.com
authors.forename: Yves
authors.initials: Y
authors.lastname: Aubert
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Allers
authors.forename: Bernd
authors.initials: B
authors.lastname: Sommer
authors.forename: E Ronald
authors.initials: ER
authors.lastname: de Kloet
authors.forename: David H
authors.initials: DH
authors.lastname: Abbott
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Datson
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002144:Callithrix / Q000502:physiology*; D004334:Drug Administration Schedule; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D056726:Genetic Association Studies; D008297:Male; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012059:Rejection, Psychology; D015203:Reproducibility of Results; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013997:Time Factors; D059467:Transcriptome
chemical_list: D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin