The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.
The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions.
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015283:Citalopram; D004542:Ejaculation / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008732:Methoxydimethyltryptamines / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000031:analogs & derivatives*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors; D015031:Zimeldine / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D011437:Propylamines; D012702:Serotonin Antagonists; D005473:Fluoxetine; D015283:Citalopram; D008711:Metergoline; D012701:Serotonin; D015031:Zimeldine; C025293:alaproclate; D000409:Alanine