title: Early-life citalopram-induced impairments in sexual behavior and the role of androgen receptor.
abstract: Postnatal treatment with selective serotonin reuptake inhibitors (SSRIs) has been found to affect brain development and the regulation of reproduction in rodent models. The normal masculinization process in the brain requires a transient decrease in serotonin (5-HT) levels in the brain during the second postnatal week. Strict regulation of androgen receptor (AR) and gonadotropin-releasing hormone (GnRH) expression is important to control male reproductive activity. Therefore, this study was designed to examine the effects of a potent SSRI (citalopram) on male sexual behavior and expression levels of AR and GnRH in adult male mice receiving either vehicle or citalopram (10mg/kg) daily during postnatal days 8-21. The citalopram-treated male mice showed altered sexual behavior, specifically a significant reduction in the number of intromissions preceding ejaculation compared with the vehicle-treated mice. The citalopram-treated male mice displayed elevated anxiety-like behavior in an open field test and lower locomotor activity in their home cage during the subjective night. Although there was no change in GnRH and AR mRNA levels in the preoptic area (POA), quantified by real-time polymerase chain reaction, immunostained AR cell numbers in the medial POA were decreased in the citalopram-treated male mice. These results suggest that the early-life inhibition of 5-HT transporters alters the regulation of AR expression in the medial POA, likely causing decreased sexual behavior and altered home cage activity in the subjective night.
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University, Sunway, Malaysia. tomoko.soga@monash.edu
authors.forename: T
authors.initials: T
authors.lastname: Soga
authors.forename: D W
authors.initials: DW
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: Putteeraj
authors.forename: K P
authors.initials: KP
authors.lastname: Song
authors.forename: I S
authors.initials: IS
authors.lastname: Parhar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D015283:Citalopram / Q000633:toxicity*; D012734:Disorders of Sex Development / Q000139:chemically induced* / Q000473:pathology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D059648:Kisspeptins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D015283:Citalopram; D012701:Serotonin; D007987:Gonadotropin-Releasing Hormone; D014365:Tryptophan Hydroxylase