Modulation of sexual behaviour in the rat by a potent and selective α 2 ‐adrenoceptor antagonist, delequamine (RS‐15385‐197)

1 . The contributions of α 2 ‐adrenoceptors and 5‐HT 1A receptors to sexual behaviour in the rat have been re‐evaluated by use of a highly potent and selective α 2 ‐adrenoceptor antagonist, delequamine (RS‐15385‐197), yohimbine, idazoxan and the partial agonist at 5‐HT 1A receptors, 8‐hydroxy‐2(di‐n‐propylamino)‐ tetralin (8‐OH‐DPAT). 2 . In a model where naive male rats were introduced to oestrogen‐progesterone primed, sexually receptive female rats, delequamine (0.4–6.4 mg kg −1 , p.o.) dose‐relatedly increased the sexual behaviour score over the entire dose‐range whereas yohimbine was effective at only one dose, 2 mg kg −1 , p.o. Idazoxan was active only at 2.5 and 5 mg kg −1 , p.o. Yohimbine, but neither delequamine nor idazoxan, decreased ejaculation latency. 8‐OH‐DPAT (0.1 and 0.25 mg kg −1 , s.c.) reduced the time, and the number of intromissions to ejaculation without affecting other parameters. A combination of delequamine (0.4 mg kg −1 , p.o.) and 8‐OH‐DPAT (0.1 mg kg −1 s.c.) increased the percentage of rats mounting, intromitting and ejaculating, and reduced ejaculation latency and the number of intromissions. 3 . In orchidectomized, sexually experienced rats exposed to sexually receptive females, delequamine, idazoxan and yohimbine increased the number of rats mounting, and there was a tendency to increase the number of animals intromitting, but no effect on ejaculatory behaviour. 4 . In ovariectomized female rats brought to low level receptivity by priming with low dose injections of oestradiol benzoate and progesterone, delequamine, at 1.6 and 6.4 mg kg −1 p.o., increased lordosis, while yohimbine, at 2, 4 and 8 mg kg −1 p.o., reduced lordotic responses to sexually experienced males in a dose‐dependent manner. 8‐OH‐DPAT at 0.1, 0.25 mg kg −1 , s.c. reduced lordosis in a dose‐dependent manner. 5 . These findings may be explained on the basis that yohimbine is an α 2 ‐adrenoceptor antagonist with affinity for 5‐HT 1A receptors and that the effects of 5‐HT 1A receptors may modulate the sexual behaviour responses to α 2 ‐receptor antagonism in some models. Thus, in contrast to yohimbine, the highly‐selective α 2 ‐adrenoceptor antagonist, delequamine, was very effective in increasing the behavioural score in male and female rats over a wide dose‐range.