Ejaculation induced by i.c.v. injection of the preferential dopamine D3 receptor agonist 7-hydroxy-2-(di-N-propylamino)tetralin in anesthetized rats

In addition to serotonin, dopamine within the CNS is known to play a primary role in the control of ejaculation. However, whether D2 and/or D3 dopamine receptor subtypes mediate this effect is still unclear. In order to clarify this issue, a pharmacological competitive study using the preferential D3 agonist 7-hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT) alone or in combination with competitive nonpreferential or preferential D2 and D3 antagonists delivered intracerebroventricularly (i.c.v.) was undertaken in anesthetized rats. Urethane-anesthetized male rats were implanted into the cerebral ventricle with a cannula for i.c.v. injections, and recording electrodes were placed within the bulbospongiosus (BS) muscle to monitor BS muscle contractions, which were used as a marker for the expulsion phase of ejaculation. Following i.c.v. injection, 7-OH-DPAT induced ejaculation and rhythmic BS muscle contractions. Co-injected i.c.v. with 7-OH-DPAT, the nonselective D2/D3 antagonist (raclopride), and the preferential D3 antagonist (S(−)-N[n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide; nafadotride) but not the preferential D2 antagonist ((±)-3-[4-(4-chlorophenyl)-4-hydroxypiperidinyl]methylindole; L 741,626) inhibited the occurrence of ejaculation and BS muscle contractions. These results suggest that i.c.v. delivery of 7-OH-DPAT does represent a pertinent model to investigate the physio-pharmacology of ejaculation. It is inferred that targeting brain D3 receptors may provide a therapeutic approach for treating ejaculatory disorders in humans.