Brain RegionSpecific Transcriptomic Markers of Serotonin1A Receptor Agonist Action Mediating Sexual Rejection and Aggression in Female Marmoset Monkeys

Abstract

IntroductionIn a marmoset model of hypoactive female sexual function, we have shown that repeated administration of the serotonin (5HT)1A agonist R(+)8hydroxy2(diNpropylamino)tetralin (8OHDPAT) inhibits sexual receptivity in female marmoset monkeys and increases aggression toward the male pairmate. AimThe aims of this study are to investigate gene expression changes induced by 8OHDPAT in lasermicrodissected brain areas that regulate female sexual function and to identify genes, functional gene classes, and pathways associated with 8OHDPATmediated inhibition of female sexual receptivity. MethodsGene expression was measured in the medial prefrontal cortex (mPFC), medial preoptic area (mPOA), cornu ammonis1 (CA1) area of the hippocampus (CA1), and dorsal raphé nucleus (DRN) of four 8OHDPATtreated (0.1 mg/kg; daily administration for 16 weeks) and four vehicletreated female marmosets using a marmosetspecific microarray (European Marmoset Microarray [EUMAMA]) and validated by realtime 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 5HT1A, 5HT2A, and 5HT7 receptors and the 5HT transporter (5HTT), was measured by RTqPCR. Main Outcome MeasuresThe main outcome is the differential expression of genes between 8OHDPAT and vehicletreated marmosets. Results8OHDPAT 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 5HTT in the DRN were strongly increased by 8OHDPAT. 5HT1A tended to increase in the mPFC, while 5HT7 was decreased in the CA1. ConclusionsBrain regionspecific alterations of gene expression regulating neural circuitries, energy demands, and learning processes are associated with 8OHDPATinduced 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.