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1 septembre 2003
Prog Neuropsychopharmacol Biol Psychiatry
1997; 21; 6; 899-922
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Role of central nitric oxide in the control of penile erection and yawning
Melis, M. R. and A. Argiolas
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Abstract :
1. Recent experimental evidence has shown that nitric oxide (NO) plays an important role in the expression of penile erection and yawning and that this molecule has to be added to the list of the best known neurotransmitters and neuropeptides involved in this symptomatology.
 
2. This was first suggested by the ability of NO synthase inhibitors injected in the lateral ventricles (i.c.v.) or in the paraventricular nucleus of the hypothalamus (PVN) to prevent these behavioral responses induced by dopamine agonists, oxytocin and NMDA. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were injected concomitantly with L-arginine, the precursor of NO. Most important, 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 synthase containing oxytocinergic neurons.
 
3. NO synthase inhibitors given i.c.v. but not in the PVN prevent also penile erection and yawning induced by ACTH and serotonin1c agonists, which induce these responses by acting with mechanisms unrelated to oxytocinergic transmission.
 
4. Dopamine agonists, NMDA and oxytocin increase NO production in the PVN at doses that induce penile erection and yawning, as determined by measuring the concentration of NO2- and NO3- in the dialyzate obtained with a vertical probe implanted in the PVN by in vivo microdialysis.
 
5. NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce penile erection and yawning indistinguishable from those induced 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 oxytocin receptor antagonist d(CH2)5-Tyr(Me)-Orn8-vasotocin, indicating that these compounds also induce penile erection and yawning by activating oxytocinergic transmission.
 
6. Finally, guanylate cyclase inhibitors (i.e. methylene blue and LY 83583) and hemoglobin injected in the PVN do not prevent rug-induced penile erection and yawning, nor 8-Br-cGMP injected in the PVN induces these behavioral responses suggesting that the mechanism by means of which endogenous or NO donor-derived NO facilitates oxytocinergic transmission to induce penile erection and yawning is not related to the activation of guanylate cyclase. Furthermore, since hemoglobin, in spite of its ability to prevent drug-induced 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 facilitate the expression of these behavioral responses.
 
no
A hypothetical mèchanism of action by means of which oxytocin, dopamine and glutamic acid (through NMDA receptors) facilitates the expression of penile erection and yawning by stimulating NO synthase in the PVN. According to this model, a group of oxytocinergic neurons projects from the PVN to extrahypothalamic brain areas (i.e. the hippocampus and/or the ventral medulla/spinal cord).
Oxytocin, dopamine and glutamic acid induce penile erection and yawning by activating these neurons the first two through the stimulation of specific receptors coupled to ornega-conotoxinsensitive Ca2+channels by a pertussis toxin-sensitive Go protein and the third one through the stimulation of Ca2+channel-coupled NMDA receptors. This would cause an influx of Ca2+ions that would activate NO-synthase. NO formed endogenously (or derived by NO donors) in turn activates yet undiscovered processes which activate oxytocinergic neurons, that induce penile erection and yawning by releasing oxytocin in areas distant from the PVN. When activated, for instance by oxytocin or dopamine, these neurons can be inhibited by opioids by a still unknown mechaninsm.
 
Yawning : role of hypothalamic paraventricular nitric oxide
Melis, M. R. and A. Argiolas
Zhongguo Yao Li Xue Bao 1999; 20; 9; 778-88
 
Yawning is a phylogenetically old, stereotyped event that occurs alone or associated with stretching and/or penile erection in humans, in animals from reptiles to birds and mammals, under different conditions. Several neurotransmitters and neuropeptides are involved in its control at the central level. One of these at the level of the paraventricular hypothalamic nucleus (PVHN) is nitric oxide (NO). First, NO synthase inhibitors injected into this hypothalamic nucleus prevent yawning induced by dopamine agonists, oxytocin or N-methyl-D-aspartic acid (NMDA), which induce yawning by activating PVHN oxytocinergic neurons projecting to extra-hypothalamic brain areas.
 
The inhibitory effect of NO synthase inhibitors was not observed when these compounds were given concomitantly with L-arginine, the precursor of NO. Second, dopamine agonists, NMDA and oxytocin given at doses that induce yawning, increase NO production in the PVHN, as determined by in vivo microdialysis. Conversely, the opiate morphine, which prevents yawning induced by dopamine agonists, oxytocin and NMDA, also prevents the increase in the paraventricular NO production induced by these compounds.
 
Third, NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce yawning when injected into the PVHN apparently by activating oxytocinergic transmission. Since guanylate cyclase inhibitors and NO scavengers (hemoglobin) injected into the PVHN do not prevent drug-induced yawning, nor 8-Br-cGMP injected into the PVHN induces this behavioral response, it is likely that NO acts as an intracellular rather than an intercellular modulator inside the PVHN oxytocinergic neurons in which NO is formed to facilitate the expression of this phylogenetically old event by guanylate cyclase-independent mechanisms.