Effects of a selective alpha 1-adrenoceptor agonist, methoxamine, on sexual behavior and penile reflexes

Methoxamine, an adrenergic agonist with selectivity for the alpha₁-adrenoceptor, when administered intraperitoneally 10 minutes prior to mating tests (1 to 5 mg/kg), effected reductions in the ejaculatory threshold, evidenced by a decrease in the number of intromissions preceding ejaculation. In mounting tests after penile anesthetization, a test which specifically assesses sexual motivation, 3 mg/kg methoxamine was without a stimulatory effect. Further, in penile reflex tests (ex copula) 1 mg/kg methoxamine was without effect, whereas 5 mg/kg decreased the number of erections, cups and flips per test, and increased the incidence of seminal emission. These data indicate a facilitation of the ejaculatory mechanism, both in and ex copula, coupled with an inhibition of erectile responses for moderate doses of methoxamine. Treatment of male rats with the alpha₂-adrenoceptor agonist clonidine (0.25 mg/kg, IP, five minutes pretest) drastically reduced the number of animals exhibiting intromissive and ejaculatory behavior in mating tests. This suppressive effect of clonidine was not prevented by prior treatment with methoxamine (3 mg/kg, 10 minutes pretest and five minutes preclonidine). Further, ST-91, a polar analog of clonidine which does not readily enter the central nervous system, was without effect on male sexual behavior. Since (1) the effects of methoxamine administration are not of similar quality or magnitude to those reported earlier after yohimbine, an alpha₂-adrenoceptor antagonist, (2) since concurrent stimulation of alpha₁- (by methoxamine) and alpha₂- (by clonidine) adrenoceptors is followed by a suppression of sexual behavior similar to that seen after clonidine alone, and (3) since a peripherally acting alpha₂-adrenoceptor agonist is without effect on sexual behavior, we suggest that one of the substrates underlying the clonidine-induced suppression of male rats' sexual behavior are postsynaptic alpha₂-adrenoceptors located within the central nervous system. Further, alpha₁-adrenoceptors appear to play a role in the regulation of the ejaculatory threshold in and ex copula, and in the regulation of erection ex copula.