Dopamine agonists increase nitric oxide production in the paraventricular nucleus of the hypothalamus: Correlation with penile erection and yawning

A low dose of apomorphine (80 mu g/kg s.c.), a mixed D1/D2 agonist that induces penile erection and yawning, increased the concentration of NO2- from 1.12 +/- 0.45 mu M to 3.8 +/- 0.75 mu M and NO3- from 5.53 +/- 0.82 to 11.25 +/- 2.30 mu M in the dialysate collected from the paraventricular nucleus of the hypothalamus of male rats by in vivo microdialysis. The NO2- concentration was also increased by LY 171555 (50 mu g/kg s.c.), a D2 agonist that induces penile erection and yawning, but not by SKF 38393 (5 mg/kg s.c.), a D1 agonist with no effect on these responses. Conversely, apomorphine's effect on NO2- was prevented by haloperidol (0.5 mg/kg i.p.), a mixed D1/D2 antagonist and L-sulpiride (25 mg/kg i.p.), a D2 antagonist, but not by the D1 agonist SCH 23390 (50 mu g/kg s.c.), although all three compounds prevented penile erection and yawning. The apomorphine effect on NO2-, penile erection and yawning was also prevented by the nitric oxide synthase inhibitor (G)(N)-nitro-L-arginine methyl ester (200 mu g i.c.v.). The nitric oxide scavenger haemoglobin (200 mu g i.c.v.) also prevented the NO2- increase, but was ineffective against penile erection and yawning. In contrast, the oxytocin antagonist d(CH2)(5)Tyr(Me)-Om(8)-vasotocin (1 mu g i.c.v.) and the guanylate cyclase inhibitor methylene blue (300 mu g i.c.v.) had no effect on the NO2- increase, but did prevent the behavioural responses. We infer from this that dopamine agonists induce penile erection and yawning by acting on D2 receptors that increase nitric oxide synthase activity in the cell bodies of paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas.