The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

In rats, the ejaculatory response and other behaviors linked to serotonin (5-HT) were tested after giving a serotonin-releasing drug (5-MeODMT) following treatment with various serotonin reuptake inhibitors (fluoxetine, zimeldine, alaproclate, citalopram). Acute doses of fluoxetine and zimeldine reduced the ejaculatory response when given 48 hours before 5-MeODMT, an effect blocked by a serotonin receptor antagonist. After 7 or 14 days, a single dose of fluoxetine enhanced the response, which returned to normal by day 24. Repeated fluoxetine treatment extended the blockade and delayed sensitization. Alaproclate and citalopram only blocked the response 1 hour after acute dosing. The findings indicate that different serotonin reuptake inhibitors do not uniformly alter serotonin receptor functions.

Study at a glance

Abstract

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.