Synergistic actions of the 5-HT1A receptor antagonist WAY-100635 and citalopram on male rat ejaculatory behavior.
The selective serotonin re-uptake inhibitor citalopram (0-40 mg kg(-1), s.c., - 60 min) did not affect the male rat ejaculatory behavior, and there were no statistically significant effects of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide 3HCl (WAY-100635) (0.04-0.08 mg kg(-1), s.c., - 30 min). When combined, there was a marked, and statistically significant, prolongation of the ejaculation latency in comparison with saline treated controls, as well as in comparison with either drug by itself. This citalopram (10.0)/WAY-100635 (0.04)-induced effect was fully antagonized by the administration of the 5-HT1B receptor antagonist isamoltane (4.0 mg kg(-1)). There were no consistent effects on other aspects of the male rat sexual behavior, i.e., number of mounts and intromissions preceding ejaculation and the post-ejaculatory interval. Finally, the intromission latency was also markedly enhanced in animals receiving both citalopram and WAY-100635, and at the higher dose of WAY-100635 (0.08 mg kg(-1)) 7 out of 18 animals failed to initiate copulation. It is suggested that blockade of inhibitory 5-HT1A autoreceptors discloses inhibitory effects of the selective serotonin re-uptake inhibitor citalopram on male rat ejaculatory behavior mediated via stimulation of 5-HT1B receptors.
Ahlenius
S
S
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden. sven.ahlenius@fyfa.ki.se
Larsson
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004542:Ejaculation / Q000187:drug effects*; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D015283:Citalopram; D010879:Piperazines; D011412:Propanolamines; D011725:Pyridines; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C058392:isamoltane