Dopamine agonists 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

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.