title: 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.
abstract: 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.
authors.affiliation: Bernard B. Brodie Department of Neuroscience and Centre of Excellence for the Neurobiology of Addictions, University of Cagliari, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Sanna
authors.forename: Salvatora
authors.initials: S
authors.lastname: Succu
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Melis
authors.forename: Antonio
authors.initials: A
authors.lastname: Argiolas
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects*; D010410:Penile Erection / Q000187:drug effects*; D000077487:Pramipexole; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D015000:Yawning / Q000187:drug effects*; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D002121:Calcium Channel Blockers; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D011954:Receptors, Dopamine; D020960:omega-Conotoxins; D002956:Citrulline; D009569:Nitric Oxide; D010121:Oxytocin; D000077487:Pramipexole; D013890:Thiourea; C086717:S-methylthiocitrulline; D001058:Apomorphine