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

Neuroscience. 2007 Mar 16;145(2):605-10. doi: 10.1016/j.neuroscience.2006.12.003. Epub 2007 Jan 29.

Abstract

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.

MeSH terms

  • Anesthetics, General / pharmacology
  • Animals
  • Dopamine / metabolism
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Dopamine D2 Receptor Antagonists
  • Drug Interactions / physiology
  • Ejaculation / drug effects
  • Ejaculation / physiology*
  • Erectile Dysfunction / drug therapy
  • Erectile Dysfunction / metabolism
  • Erectile Dysfunction / physiopathology
  • Genitalia, Male / innervation
  • Genitalia, Male / physiology*
  • Injections, Intraventricular
  • Male
  • Models, Biological
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology*
  • Rats
  • Rats, Wistar
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / agonists
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D3 / metabolism*
  • Tetrahydronaphthalenes / pharmacology*
  • Urethane / pharmacology

Substances

  • Anesthetics, General
  • Dopamine Agonists
  • Dopamine Antagonists
  • Dopamine D2 Receptor Antagonists
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Tetrahydronaphthalenes
  • Urethane
  • 7-hydroxy-2-N,N-dipropylaminotetralin
  • Dopamine