Role of nitric oxide in penile erection and yawning induced by 5-HT_1c receptor agonists in male rats

Abstract

The effect of the intracerebroventricular (i.c.v.) administration of N^G-nitro-l,-arginine methyl ester and N^G-monomethyl-l.-arginine, two inhibitors of nitric oxide (NO) synthase, on penile erection and yawning induced by 1-(3-chlorophenyl)-piperazine (m-CPP)- and N-(3-trifluoromethylphenyl)-piperazine (TFMPP), two selective 5HT_1c receptor agonists, was studied in male rats. Both NO synthase inhibitors (50–500 μg i.c.v.) prevented dose-dependently the behavioural responses induced by m-CPP (0.5 mg/kg s.c.) or by TFMPP (I mg/kg s.c.), but N^G-nitro-l-arginine methyl ester was about 4–5 times more potent than N^G-monomethyl-l,-arginine. The D-isomer of N_G-monomethyl-l-arginine, which does not inhibit nitric oxide synthase, was ineffective. The inhibitory effect of N^G-nitro-l-arginine methyl ester on m-CPP- and TFMPP-induced responses was prevented by the administration of l-arginine (1 mg i.c.v.). In contrast, N^G-nitro-l-arginine methyl ester (20 μg) was ineffective when injected in the paraventricular nucleus of the hypothalamus, a brain area that plays a key role in the expression of these behavioural responses. m-CPP- and TFMPP-induced penile erection and yawning was prevented also by the i.c.v. administration of LY 83583 (50–200 μg) or methylene blue (50–400 μg), two inhibitors of guanylate cyclase but not by reduced hemoglobin (50–400 μg), a NO scavenger. The results suggest that central nitric oxide is involved in the expression of penile erection and yawning induced by 5-HT_1c receptor agonists.