Oxytocin increases nitric oxide production in the paraventricular nucleus of the hypothalamus of male rats: Correlation with penile erection and yawning

A dose of oxytocin (50 ng i.c.v.) that induces penile erection and yawning, increased the concentration of NO2- from 0.98 +/- 0.29 to 4.2 +/- 0.79 mu M and of NO3- from 5.6 +/- 0.33 to 12.03 +/- 0.99 mu M in the dialysate from the paraventricular nucleus of the hypothalamus of male rats, as measured by in vivo microdialysis. NO2- concentration was also increased by [Thr(4),Gly(7)]-oxytocin (100 ng i.c.v.) and oxytocin(1-8) (1 mu g i.c.v.), which also induced penile erection and yawning, but not by oxytocin(1-6) (1 mu g i.c.v.) or oxytocin(7-9) (1 mu g i.c.v.), which were unable to induce these behavioral responses. The oxytocin effect on NO2- concentration, penile erection and yawning was prevented by the oxytocin receptor antagonist, d(CH2)(5)Tyr(Me)-Orn(8)-vasotocin (1 mu g i.c.v.), or by the nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl eater (200 mu g i.c.v.), but not by the dopamine receptor antagonist, haloperidol (0.5 mg/kg i.p.). The nitric oxide scavenger, hemoglobin (200 mu g i.c.v.), prevented oxytocin-induced NO2- concentration increase, but was unable to prevent penile erection and yawning. Methylene blue (300 mu g i.c.v.), an inhibitor of guanylate cyclase, was ineffective on oxytocin-induced NO2- concentration increase, but, prevented the behavioral responses. The results suggest that oxytocin induces penile erection and yawning by increasing nitric oxide synthase activity in the cell bodies of oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating the behavioral responses. (C) 1997 Elsevier Science B.V.