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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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Arcuate Nucleus of Hypothalamus / drug effects
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Arcuate Nucleus of Hypothalamus / metabolism
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Arcuate Nucleus of Hypothalamus / pathology
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Citalopram / administration & dosage
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Citalopram / pharmacology*
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Drug Therapy, Combination
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Ejaculation / drug effects*
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Genes, fos / drug effects
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Genes, fos / genetics
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Immunohistochemistry / methods
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Injections, Subcutaneous
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Male
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Piperazines / administration & dosage
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Piperazines / pharmacokinetics*
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Proto-Oncogene Proteins c-fos / drug effects
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / immunology*
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Pyridines / administration & dosage
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Pyridines / pharmacokinetics*
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Rats
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Rats, Wistar
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Receptor, Serotonin, 5-HT1A / administration & dosage
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Serotonin 5-HT1 Receptor Antagonists
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Sexual Behavior, Animal / drug effects
Substances
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Piperazines
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Proto-Oncogene Proteins c-fos
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Pyridines
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Serotonin 5-HT1 Receptor Antagonists
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Citalopram
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Receptor, Serotonin, 5-HT1A
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N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide