TY - JOUR T1 - Central Mechanisms Regulating Penile Erection in Conscious Rats: The Dopaminergic Systems Related to the Proerectile Effect of Apomorphine JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 330 LP - 338 DO - 10.1124/jpet.103.057455 VL - 308 IS - 1 AU - Gin C. Hsieh AU - Peter R. Hollingsworth AU - Brenda Martino AU - Renjie Chang AU - Marc A. Terranova AU - Alyssa B. O'Neill AU - James J. Lynch AU - Robert B. Moreland AU - Diana L. Donnelly-Roberts AU - Teodozyi Kolasa AU - Joseph P. Mikusa AU - Jill M. McVey AU - Kennan C. Marsh AU - James P. Sullivan AU - Jorge D. Brioni Y1 - 2004/01/01 UR - http://jpet.aspetjournals.org/content/308/1/330.abstract N2 - Apomorphine has been used as a pharmacological probe of dopaminergic receptors in a variety of central nervous system disorders. The utility of apomorphine as an agent for the treatment of erectile dysfunction has also been demonstrated clinically. Apomorphine is a nonselective dopaminergic receptor agonist with potent binding affinity (Ki) of 101, 32, 26, 2.6, and 10 nM for D1, D2, D3, D4, and D5, respectively. When administered either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.), apomorphine fully evoked penile erections in conscious rats with maximum effect at 0.1 μmol/kg s.c. and 3 nmol/rat i.c.v., respectively. Apomorphine was less efficacious when injected intrathecally (i.t.) to L4-L6 spinal levels (50% at 30–100 nmol/rat i.t.). Penile erection facilitated by apomorphine was blocked by haloperidol and clozapine (i.p. and i.c.v.) but not by domperidone (a peripherally acting dopaminergic receptor antagonist). In this model using conscious rats, penile erection was significantly induced by quinpirole (D2-D3-D4 receptor agonist), but not by R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF38393) and R(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzapine (SKF81297) (D1 receptor agonists), or a D2 receptor agonist R-5,6-dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine (PNU-95666E). The role of D4 receptors in penile erection was demonstrated using selective D4 receptor agonists [(4-phenylpiperazinyl)-methyl]benzamide (PD168077) and 5-fluoro-2-{[4-(2-pyridinyl)-1-piperazinyl]methyl}-1H-indole (CP226269), whether administered systemically (s.c.) or locally in the brain (i.c.v.). The ability of apomorphine to activate D3 receptors in relation to its proerectile activity remains to be elucidated by use of selective subtype agonists. These results suggest that the proerectile action of apomorphine in rats is mediated at supraspinal levels and that this effect is not mimicked by a D2 receptor agonist but associated with activation of D4 receptors. The American Society for Pharmacology and Experimental Therapeutics ER -