ROLE OF CENTRAL NITRIC-OXIDE IN THE CONTROL OF PENILE ERECTION AND YAWNING

1. Recent experimental evidence has shown that nitric oxide (NO) plays an important role in the expression of penile erection and yawning an d that this molecule has to be added to the list of the best known neu rotransmitters and neuropeptides involved in this symptomatology. 2. T his was first suggested by the ability of NO synthase inhibitors injec ted in the lateral ventricles (i.c.v.) or in the paraventricular nucle us of the hypothalamus (PVN) to prevent these behavioral responses ind uced by dopamine agonists, oxytocin and NMDA. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were inj ected concomitantly with L-arginine, the precursor of NO. Most importa nt, this hypothalamic nucleus is one of the richest brain areas of NO synthase and also the brain site where dopamine, NMDA and oxytocin act to induce penile erection and yawning by activating central NO syntha se containing oxytocinergic neurons. 3. NO synthase inhibitors given i .c.v, but not in the PVN prevent also penile erection and yawning indu ced by ACTH and serotonin,, agonists, which induce these responses by acting with mechanisms unrelated to oxytocinergic transmission. 4. Dop amine agonists, NMDA and oxytocin increase NO production in the PVN at doses that induce penile erection and yawning, as determined by measu ring the concentration of NO2 . and NO3 . in the dialyzate obtained wi th a vertical probe implanted in the PVN by in vivo microdialysis. 5. NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylami ne, induce penile erection and yawning indistinguishable from those in duced by oxytocin, dopamine agonists or NMDA when injected in the PVN. The NO donor response was prevented by the i.c.v. injection of the ox ytocin receptor antagonist d(CH2)(5)-Tyr(Me)-Orm(8)-vasotocin, indicat ing that these compounds also induce penile erection and yawning by ac tivating oxytocinergic transmission. 6. Finally, guanylate cyclase inh ibitors (i.e. methylene blue and LY 83583) and hemoglobin injected in the PVN do not prevent drug-induced penile erection and yawning, nor 8 -Br-cGMP injected in the PVN induces these behavioral responses sugges ting that the mechanism by means of which endogenous or NO donor-deriv ed NO facilitates oxytocinergic transmission to induce penile erection and yawning is not related to the activation of guanylate cyclase. Fu rthermore, since hemoglobin, in spite of its ability to prevent drug-i nduced NO production in the PVN, does not prevent penile erection and yawning, it is likely that NO acts as an intracellular rather than an intercellular modulator in the PVN neurons in which is formed to facil itate the expression of these behavioral responses. (C) 1997 Elsevier Science Inc.