title: Citalopram combined with WAY 100635 inhibits ejaculation and ejaculation-related Fos immunoreactivity.
abstract: The role of 5-HT (5-hydroxytryptamine, 5-HT)(1A) receptor activation in the sexual side-effects, in particular delayed ejaculation, of selective serotonin reuptake inhibitors (SSRIs) was studied. Male Wistar rats were treated for 15 days with vehicle, the SSRI citalopram (10 mg/kg/day p.o.), the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCL (WAY 100635, 0.1 mg/kg/ day s.c.), or both drugs combined. Sexual behavior was assessed weekly. One h after the last sexual behavior test, rat brains were processed for Fos-immunohistochemistry. Acute and chronic citalopram mildly inhibited ejaculation, which was strongly augmented by co-administration of WAY 100635. WAY 100635 alone did not alter sexual behavior. Brain sites associated with ejaculation showed reduced Fos-immunoreactivity in rats treated with both citalopram and WAY 100635. Citalopram reduced Fos-immunoreactivity in the arcuate hypothalamic nucleus, an area that might link serotonergic neurotransmission to ejaculation.
authors.affiliation: Department of Anatomy, University Medical Centre St. Radboud, Nijmegen, The Netherlands. t.dejong@pnf.umcn.nl
authors.forename: Trynke R
authors.initials: TR
authors.lastname: de Jong
authors.forename: Tommy
authors.initials: T
authors.lastname: Pattij
authors.forename: Jan G
authors.initials: JG
authors.lastname: Veening
authors.forename: P Jos W C
authors.initials: PJ
authors.lastname: Dederen
authors.forename: Marcel D
authors.initials: MD
authors.lastname: Waldinger
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Cools
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004542:Ejaculation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D007279:Injections, Subcutaneous; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000008:administration & dosage; D058829:Serotonin 5-HT1 Receptor Antagonists; D012726:Sexual Behavior, Animal / Q000187:drug effects
chemical_list: D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide