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

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. 1986 British Pharmacological Society