Dopamine agonist-induced penile erection and yawning: differential role of D₂-like receptor subtypes and correlation with nitric oxide production in the paraventricular nucleus of the hypothalamus of male rats

Behav Brain Res. 2012 May 1;230(2):355-64. doi: 10.1016/j.bbr.2012.02.033. Epub 2012 Feb 25.


The dopamine D₃ preferring agonist pramipexole (50 ng) induced penile erection and yawning when injected into the paraventricular nucleus of the hypothalamus of male rats, like the mixed D₁/D₂-like agonist apomorphine (50 ng), while the D₄ agonist PD 168,077 (100 ng), induced penile erection only. These responses lasted for 45-60 min and occurred with an increase of NO₂- and NO₃- concentrations in the dialysate obtained from the paraventricular nucleus by intracerebral microdialysis. Pramipexole and apomorphine responses were reduced by the D₂ preferring antagonist L-741,626 (5 μg), but not by the D₃ preferring antagonist SB-277011A (10 μg), or the D₄ preferring antagonist L-745,870 (5 μg), injected into the PVN before the dopamine agonist. In contrast, PD 168,077 responses were reduced by L-745,870, but not by L-741,626 or SB-277011A. Pramipexole, apomorphine and PD 168,077 effects were also reduced by the nitric oxide synthase inhibitor S-methyl-L-thiocitrulline (20 μg) and the N-type voltage-dependent Ca²⁺ channels blocker ω-conotoxin (5 ng), given into the paraventricular nucleus, and by the oxytocin antagonist d(CH₂)₅Tyr(Me)²-Orn⁸-vasotocin (2 μg), given intracerebroventricularly but not into the paraventricular nucleus before dopamine agonists. These results suggest that stimulation of D₂, but not D₃ or D₄ receptors, by pramipexole or apomorphine increases Ca²⁺ influx in cell bodies of oxytocinergic neurons. This increases the production of nitric oxide, which activates oxytocinergic neurotransmission in extra-hypothalamic brain areas and spinal cord, leading to penile erection and yawning. However, the stimulation of D₄ receptors by PD 168,077 also increases Ca²⁺ influx/nitric oxide production leading to penile erection, but not yawning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Benzothiazoles / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Citrulline / analogs & derivatives
  • Citrulline / pharmacology
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Male
  • Microdialysis
  • Nitric Oxide / analysis
  • Nitric Oxide / biosynthesis*
  • Oxytocin / antagonists & inhibitors
  • Oxytocin / pharmacology
  • Paraventricular Hypothalamic Nucleus / drug effects*
  • Penile Erection / drug effects*
  • Pramipexole
  • Rats
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / physiology*
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology
  • Yawning / drug effects*
  • omega-Conotoxins / pharmacology


  • Benzothiazoles
  • Calcium Channel Blockers
  • Dopamine Agonists
  • Dopamine Antagonists
  • Enzyme Inhibitors
  • Receptors, Dopamine
  • omega-Conotoxins
  • Citrulline
  • Nitric Oxide
  • Oxytocin
  • Pramipexole
  • Thiourea
  • S-methylthiocitrulline
  • Apomorphine