1. The contributions of alpha 2-adrenoceptors and 5-HT1A receptors to sexual behaviour in the rat have been re-evaluated by use of a highly potent and selective alpha 2-adrenoceptor antagonist,
delequamine (RS-15385-197),
yohimbine,
idazoxan and the partial agonist at 5-HT1A 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 alpha 2-adrenoceptor antagonist with affinity for 5-HT1A receptors and that the effects of 5-HT1A receptors may modulate the sexual behaviour responses to alpha 2-receptor antagonism in some models. Thus, in contrast to
yohimbine, the highly-selective alpha 2-adrenoceptor antagonist,
delequamine, was very effective in increasing the behavioural score in male and female rats over a wide dose-range.