TY - JOUR T1 - Proerectile Effects of Dopamine D<sub>2</sub>-Like Agonists Are Mediated by the D<sub>3</sub> Receptor in Rats and Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 210 LP - 217 DO - 10.1124/jpet.108.144048 VL - 329 IS - 1 AU - Gregory T. Collins AU - Andrew Truccone AU - Faiza Haji-Abdi AU - Amy Hauck Newman AU - Peter Grundt AU - Kenner C. Rice AU - Stephen M. Husbands AU - Benjamin M. Greedy AU - Cecile Enguehard-Gueiffier AU - Alain Gueiffier AU - Jianyong Chen AU - Shaomeng Wang AU - Jonathan L. Katz AU - David K. Grandy AU - Roger K. Sunahara AU - James H. Woods Y1 - 2009/04/01 UR - http://jpet.aspetjournals.org/content/329/1/210.abstract N2 - Dopamine D2-like agonists induce penile erection (PE) and yawning in a variety of species, effects that have been suggested recently to be specifically mediated by the D4 and D3 receptors, respectively. The current studies were aimed at characterizing a series of D2, D3, and D4 agonists with respect to their capacity to induce PE and yawning in the rat and the proerectile effects of apomorphine [(R)-(-)-5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo-[de,g]quinoline-10,11-diol hydrochloride] in wild-type and D4 receptor (R) knockout (KO) mice. All D3 agonists induced dose-dependent increases in PE and yawning over a similar range of doses, whereas significant increases in PE or yawning were not observed with any of the D4 agonists. Likewise, D2, D3, and D4 antagonists were assessed for their capacity to alter apomorphine- and pramipexole (N′-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine dihydrochloride)-induced PE and yawning. The D3 antagonist, PG01037 [N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide hydrochloride], inhibited the induction of PE and yawning, whereas the D2 antagonist, L-741,626 [3-[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1H-indole], reversed the inhibition of PE and yawning observed at higher doses. The D4 antagonist, L-745,870 [3-(4-[4-chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo[2,3-b]pyridine trihydrochloride], did not alter apomorphine- or pramipexole-induced PE or yawning. A role for the D3 receptor was further supported because apomorphine was equipotent at inducing PE in wild-type and D4RKO mice, effects that were inhibited by the D3 antagonist, PG01037, in both wild-type and D4R KO mice. Together, these studies provide strong support that D2-like agonist-induced PE and yawning are differentially mediated by the D3 (induction) and D2 (inhibition) receptors. These studies fail to support a role for the D4 receptor in the regulation of PE or yawning by D2-like agonists. U.S. Government work not protected by U.S. copyright ER -