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

The dopamine D-3 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 D-1/D-2-like agonist apomorphine (50 ng), while the D-4 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 D-2 preferring antagonist L-741,626 (5 mu g), but not by the D-3 preferring antagonist SB-277011A (10 mu g), or the D-4 preferring antagonist L-745,870 (5 mu g), 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 mu g) and the N-type voltage-dependent Ca2+ channels blocker omega-conotoxin (5 ng), given into the paraventricular nucleus, and by the oxytocin antagonist d(CH2)(5)Tyr(Me)(2)-Orn(8)-vasotocin (2 mu g), 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 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 D-4 receptors by PD 168,077 also increases Ca2+ influx/nitric oxide production leading to penile erection, but not yawning. (C) 2012 Elsevier B.V. All rights reserved.