Penile erection and yawning induced by dopamine D2-like receptor agonists in rats: influence of strain and contribution of dopamine D2, but not D3 and D4 receptors.
Dopamine (DA) is implicated in penile erection (PE) and yawning (YA) in rats through activation of D2-like receptors. However, the exact role of each subtype (D2, D3 and D4) of this receptor family in PE/YA is still not clearly elucidated. We recorded concomitantly PE and YA after treatment with agonists with various levels of selectivity for the different subtypes of D2-like receptors. In addition, we investigated the efficacy of antagonists with selective or preferential affinity for each of the three receptor subtypes to prevent apomorphine-induced PE and YA. Wistar rats were more sensitive than Long-Evans rats to the erectogenic activity of the nonselective DA agonist apomorphine (0.01-0.08 mg/kg), whereas Sprague-Dawley rats were insensitive. However, all the three strains were equally sensitive to apomorphine-induced YA. In Wistar rats, apomorphine (0.01-0.63 mg/kg), the D2/D3 agonists quinelorane and (+)7-OH-DPAT (0.000625-10 mg/kg) or PD 128,907 (0.01-10 mg/kg), but not the D4 agonists PD-168,077, RO-10-5824 and ABT-724 (0.04-0.63 mg/kg), produced PE and YA with bell-shaped dose-response curves. Similarly, ABT-724 and CP226-269 (another D4 agonist) failed to elicit PE and YA in Sprague-Dawley rats. Furthermore, in Wistar rats, PE and YA elicited by apomorphine (0.08 mg/kg) were not modified by selective D3 (S33084 and SB-277011, 0.63-10 mg/kg) or D4 (L-745,870 and RBI-257, 0.63-2.5 mg/kg) antagonists, but were prevented by the preferential D2 blocker L-741,626 (near-full antagonism at 2.5 mg/kg). The present data do not support a major implication of either DA D3 or D4 receptors in the control of PE and YA in rats, but indicate a preponderant role of DA D2 receptors.
Depoortère
Ronan
R
Division of Neurobiology 2, Centre de Recherche Pierre Fabre, Castres, France. ronan.depoortere@pierre-fabre.com
Bardin
Laurent
L
Rodrigues
Michael
M
Abrial
Erika
E
Aliaga
Monique
M
Newman-Tancredi
Adrian
A
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors; D050638:Receptors, Dopamine D4 / Q000819:agonists* / Q000037:antagonists & inhibitors; D013045:Species Specificity; D015000:Yawning / Q000187:drug effects*
D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D001058:Apomorphine