Ejaculation induced by i.c.v. injection of the preferential dopamine D(3) 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 D(2) and/or D(3) dopamine receptor subtypes mediate this effect is still unclear. In order to clarify this issue, a pharmacological competitive study using the preferential D(3) agonist 7-hydroxy-2-(di-N-propylamino)tetralin (7-OH-DPAT) alone or in combination with competitive nonpreferential or preferential D(2) and D(3) 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 D(2)/D(3) antagonist (raclopride), and the preferential D(3) antagonist (S(-)-N[n-butyl-2-pyrrolidinyl)methyl]-1-methoxy-4-cyanonaphtalene-2-carboxamide; nafadotride) but not the preferential D(2) 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 D(3) receptors may provide a therapeutic approach for treating ejaculatory disorders in humans.
Clément
P
P
Pelvipharm Laboratories, Centre National de la Recherche Scientifique, Batiment 5, avenue de la Terrasse, 91190 Gif-sur-Yvette, France.
Bernabé
J
J
Denys
P
P
Alexandre
L
L
Giuliano
François
F
D018681:Anesthetics, General / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions / Q000502:physiology; D004542:Ejaculation / Q000187:drug effects / Q000502:physiology*; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005837:Genitalia, Male / Q000294:innervation / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014520:Urethane / Q000494:pharmacology
D018681:Anesthetics, General; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D014520:Urethane; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine