Dopamine agonist-induced penile erection and yawning: Differential role of D 2-like receptor subtypes and correlation with nitric oxide production in the paraventricular nucleus of the hypothalamus of male rats

摘要

The dopamine D 3 preferring agonist pramipexole (50ng) induced penile erection and yawning when injected into the paraventricular nucleus of the hypothalamus of male rats, like the mixed D 1/D 2-like agonist apomorphine (50ng), while the D 4 agonist PD 168,077 (100ng), induced penile erection only. These responses lasted for 45-60min and occurred with an increase of NO 2- and NO 3- concentrations in the dialysate obtained from the paraventricular nucleus by intracerebral microdialysis. Pramipexole and apomorphine responses were reduced by the D 2 preferring antagonist L-741,626 (5μg), but not by the D 3 preferring antagonist SB-277011A (10μg), or the D 4 preferring antagonist L-745,870 (5μg), 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 (20μg) and the N-type voltage-dependent Ca 2+ channels blocker ω-conotoxin (5ng), given into the paraventricular nucleus, and by the oxytocin antagonist d(CH 2) 5Tyr(Me) 2-Orn 8-vasotocin (2μg), given intracerebroventricularly but not into the paraventricular nucleus before dopamine agonists. These results suggest that stimulation of D 2, but not D 3 or D 4 receptors, by pramipexole or apomorphine increases Ca 2+ 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 D 4 receptors by PD 168,077 also increases Ca 2+ influxitric oxide production leading to penile erection, but not yawning.