The effects of 5HT1 agonists on erection in rats in vivo and rabbit corpus cavernosum in vitro

Abstract

We have examined the effects of the selective 5-HT1a and 5-HT1b agonists 8-hydroxy-2-(di-n- propylamino)tetralin (8.OHDPAT) and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2- a]quinoxaline (CGS12066b), respectively on erection in rats in vivo and rabbit corpus cavernosum in vitro. Apomorphine (0.1 mg/kg) induced 3.1 ± 0.4 erections in vehicle-pretreated animals. At the highest doses tested 8-OHDPAT (0.4-0.64 mg/kg) and CGS12066b (1.0-10.0 mg/kg) significantly reduced apomorphine erection to 0.9 ± 0.3 erections and 0.5 ± 0.2 erections respectively. The nonselective 5-HT agonist metachlorophenylpiperazine (m-CPP; 0.1 mg/kg) elicited characteristic increases in cavernous nerve activity (CNA) and intracavernous pressure responses (ICP) in anesthetized rats. 8-OHDPAT (0.64 mg/kg) and CGS12066b (1.0 mg/kg) failed to elicit CNA or ICP responses. CGS12066b reduced ICP responses resulting from the direct stimulation of the cavernous nerve whereas 8-OHDPAT did not. CGS12066b reduced the CNA and ICP responses to m-CPP administration whereas 8-OHDPAT potentiated m-CPP induced CNA and ICP responses. In isolated rabbit corpus cavernosum (CC) 8-OHDPAT and CGS12066b both failed to alter noradrenergic induced contraction and non-adrenergic non-cholinergic relaxation. Our results indicate that selective 5-HT1a and 5-HT1b agonists have different effects in different models of erection.