Dopamine, erectile function and sexual behavior: last discoveries and possible advances

Among neurotransmitters involved in the control of erectile function and sexual behavior, dopamine is one of the most studied. Since the first pioneering studies done in the nineteen sixties, which revealed the facilitatory role of this neurotransmitter in sexual behavior, today it is well accepted that dopamine is deeply involved in both the anticipatory (appetitive and rewarding) and consummatory (penile erection and ejaculation) phases of sexual behavior. Dopamine influences sexual behavior by acting at the level of several brain areas (i.e., medial preoptic area, paraventricular nucleus of the hypothalamus and ventral tegmental area that contains the cell bodies of mesolimbic dopaminergic neurons projecting to the nucleus accumbens). The facilitation of sexual function by dopamine is mediated mainly by the stimulation of receptors of the D2 family (D2, D3 and D4), with only a minor role for those of the D1 family (D1 and D5). In spite of the large amount of preclinical studies showing a facilitatory role of D2-like receptors in sexual behavior, scarce success was obtained with classic D2-like agonists (mainly apomorphine), especially when compared to that obtained with locally acting phosphodiesterase type V inhibitors, in the treatment of erectile dysfunction in humans. The discovery of selective D4 receptor agonists able to induce penile erection with potency similar to that of classic mixed D2 agonists in male rats has reopened the research aimed at the identification of dopamine agonists useful for the treatment of erectile dysfunction in humans. This review summarizes the most recent findings on the role of central D2, D3 and D4 receptors on erectile function and sexual behavior. These studies suggest that D4 receptors may represent a valuable therapeutic target for the therapy of erectile dysfunction.