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mise à jour du
14 août 2003
Euro J Pharmacol
1989;164:565-570
lexique
Evidence that apomorphine induces penile erection and yawning by releasing oxytocin in the central nervous system
MR Melis, A Argiolas, GLGessa
Department of Neurosciences, University of Cagliari, Italy
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren

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Introduction : Repeated episodes of penile erection and yawing can be induced in rats by either central admintration of nanogram amounts of oxytocin or by systemic or central injection of low doses of dopamine (DA) agonists such as apomorphine. Recent studies from our laboratory indicate that a neuronal DA-oxytocin link involved in the expression of the above behavioral responses exists in the central nervous system. In particular, DA agonists seem to induce yawning and penile erection by releasing oxytocin in the paraventricular nucleus of the hypothalamus (PVN) or surrounding structures.
 
Accordingly,
- the PVN bas been found to be the most sensitive brain area for the induction of penile erection and yawning induced by either oxytocin or DA agonists,
- electrolytic lesion of the PVN prevents the above behavioral responses induced by either oxytocin or apomorphine,
- blockade of DA receptors abolishes penile erection and yawning induced by DA agonists but not by oxytocin,
- i.c.v. injection of the potent oxytocin antagonist [d(CH,),-Tyr(Me)Orn8]vasotocin prevents penile erection and yawning induced not only by oxytocin, but also by apomorphine.
 
In order to provide evidence that apomorphine and oxytocin are acting by a common mechanism, we studied the effect of concomitant administration of apomorphine and oxytocin on the induction of penile erection and yawning, and compared the ability of oxytocin antagonists with different affinities for oxytocin receptors to prevent these behavioral responses induced by oxytocin and apomorphine.
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Discussion : The present results show that the effect of oxytocin and apomorphine to induce yawning and penile erection are not additive and are prevented in a dose-dependent manner by oxytocin antagonists, with the same rank order of potency as that reported for their antagonism at oxytocin receptors. Taken together, the lack of an additive effect of oxytocin and apomorphine on penile erection and yawning and the correlation between the potency in blocking oxytocin receptors and apomorphine responses suggest that the two substances are acting by a common mechanism, i.e. the apomorphine effect is mediated by the release of endogenous oxytocin. The present results confirrn and extend our previous observations showing that
-(1) oxytocin- and apomorphine-induced penile erection and yawning are prevented in a dose-dependent manner by a potent oxytocin antagonist
-(2) the oxytocin effect is not antagonized by DA receptors blockers, unlike the apomorphine-induced responses
-(3) destruction of oxytocin-containing neurons within the brain and spinal cord by electrolytic lesion of the PVN abolishes apomorphine-induced penile erection and yawning.
 
The hypothesis that apomorphine and dopaminomimetic drugs induce the behavioral responses described above by releasing oxytocin is in agreement with the results of in vivo and in vitro studies showing that DA has an excitatory role in oxytocin release. Accordingly,
(1) in vitro studies have shown that hypothalarnic tissue incubated with nanomolar concentrations of DA or apomorphine releases oxytocin into the incubation medium in much higher amounts than that released by control tissue
- (2) microiontophoretically applied DA excites oxytocinergic neurons
- (3) systemic injection of low doses of apomorphine increases plasma oxytocin levels in male rats. However, the possibility that apomorphine acts by other mechanisms cannot be ruled out completely. For instance, the drug might also alter the metabolisrn of oxytocin or oxytocin binding to its receptor, but no experimental evidence that favors these hypotheses is available at present.
As to the mechanism by which apomorphine and oxytocin induce penile erection and yawning, it is noteworthy that the PVN has been found to be the brain area that is most sensitive for the induction of penile erection and yawning by either apomorphine or oxytocin. Moreover, this nucleus contains not only the cell bodies of the magnocellular and parvocellular oxytocinergic neurons, which project to the neurohypophysis and to several extrahypothalamic brain areas, respectively, but also the cell bodies of dopaminergic neurons of the A14 group. Together with those of the groups A11 and A13, these DA neurons innervate the PVN and surrounding structures and constitute the so-called incerto-hypothalamic DA system. Finally, immunocytochemical studies have shown that DA neurons in the PVN are located mainly in the proximity of oxytocinergic neurons . The mechanism by which oxytocin induces penile erection and yawning by acting in the PVN is unknown and it is only possible to speculate about this at present. A possibility is that oxytocin activates its own neurons.
 
To support this
- (1) oxytocin receptors have been found in the PVN
- (2) locally applied oxytocin has been shown to enhance in vivo the electrical activity of oxytocinergic neurons and to stimulate in vitro the release of endogenous oxytocyn
- (3) oxytocin-immunoreactive synapses have been found to impinge on oxytocinergic neurons in hypothalamic nuclei.
Our results provide further evidence for a neurotransmitter role for oxytocin in the central nervous system. Indeed, oxytocin has been implicated in, apart from the induction of penile erection and yawning, the modulation of memory and learning processes, maternal behaviour, copulatory behaviour, tolerance and dependence mechanisms and may be the precursor of potent behaviourally active neuropeptides.
-Tang AH, Himes CS Apomorphine produced more yawning in Sprague-Dawley rats than in F344 rats: a pharmacological study Eur J Pharmacol 1995; 284; 1-2; 13-18