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mise à jour
du 15 juillet 2004
Europ J Pharmacol
Oxytocin: an extremely potent inducer
of penile erection and yawning in male rats 
Argiolas A, Melis MR, Gessa GL
Department of neuroscience Cagliari University Italy
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


Introduction :
The central administration of adrenocortiin (ACTH) and a-melanocyte-stimulating one (a-MSH) induces excessive grooming and a peculiar syndrome characterized by recurrent episodes of yawning, stretching, penile erection and ejaculation. While grooming is also induced peptides, the above syndrome is considered to be specific for ACTH-MSH peptides, since it is not induced by any other know peptide tested. Moreover, early work from our group has shown that the total peptide extract from a few rat hypothalami produced the above syndrome when injected into the lateral ventricle of a recipient rabbit (Bertolini et al., 1975).
This finding was surprising, since the total hypothalamic content of the whole combination ACTH and MSH is about 1000 times lower than the minimum dose of these peptides necessary to induce the above-mentioned effects. This raised the possibility that some other active substance might be present in the hypothalamus in addition to ACTH and a-MSH. In order to test this hypothesis, we fractionated the total peptide extract from the rat hypothalamus by high pressure liquid chrornatography (HPLQ and tested each fraction for its ability to induce yawning, streching and penile erection. Here we report that another peptide is present in the hypothalamus which is capable of inducing yawning and penile erection in rats with a potency of at least 500 times that of ACTH and a-MSH. This peptide is oxytocin
Discussion: The present results show that the i.c.v. administration of minute amounts of oxytocin produced repeated episodes of penile erection and yawning. Moreover, among the 45 hypothalarnic fractions separated by HPLC from the whole extract from 50 hypothalami, only that corresponding to oxytocin was found to be active in producing penile erection and yawning. Finally, synthetic oxytocin proved to be a most potent agent capable of producing the above responses. Our data support the idea that oxytocin, besides its known hormonal actions in the periphery, might act as a neuropeptide in the central nervous system. Indeed, oxytocin is synthetized in neurons originating in the hypothalamus that send their projections not only to the neurohypophysis, but also to other brain areas, such as amygdala, frontal cortex, lateral septum, hippocampus, pons and medulla, with an innervation different from that of the other neurohypophyseal. peptide vasopressin. Moreover, oxytocin receptors have been demonstrated in rat brain Furthermore, oxytocin has been implicated in the modulation of memory processes, in the induction of maternal behaviour and in the development of narcotic tolerance and physical depenilence. Finally, oxytocin seems to be the precursor of other potent biologically active neuropeptides.
Our results suggest that oxytocin is implicated in the regulation of yawning and penile erection. Since our results have shown that oxytocin has a bell-shaped dose-response curve, it is possible that the failure of previous studies to observe penile erection and yawning was due to the fact that the doses used were too high. The reason for such biphasic response is not known, although. similar inverted U-shaped doseresponse curves have been reported for other behavioural effects of oxytocin. As te, the relationship between yawning and sexual arousal, it is pertinent to recall that yawning and stretching have been considered an evolutionary vestige of behaviour subservient to arousal when attention is decreasing in face of danger, that yawning may be displayed by male animals as a sign of dominance and that yawning is often displayed by primates during sexual arousal.

So far only two means have been available to induce both penile erection and yawning in experimental animals. One is the systemic administration of apomorphine and other dopamine receptor agonists; the second is the injection of ACTH-MSH peptides into the cerebrospinal fluid or into specific brain areas. The present results indicate that oxytocin is another agent capable of inducing penile erection and yawning. However, two important features distinguish the oxytocin effect from that of ACTH-MSH peptides: a far greater potency (5-60 µmol versus 2 nmol, respectively), and a much shorter delay in the onset of the symptomatology (penile erection and yawning begin after a lag of 5-10 min and 25-30 min after i.c.v. oxytocin and ACTH-MSH peptides, respectively). Such features led us to speculate that ACTH-MSH peptides, or doparninomimetic drugs, produce yawning and penile erection by releasing oxytocin in some brain area. Accordingly, the pharmacological interactions studied so far, indicate that the site of action of oxytocin is situated downhill with respect to that of dopamine agonists. In fact, the oxytocin response as well as that of ACTH-MSH peptides is not antagonized by haloperidol in doses which were found to completely suppress the action of apomorphine and other dopamine receptor agonists. However, so far it has not been possible to obtain pharmacological differentiation of oxytocin- and ACTH-induced responses. Indeed, both morphine and atropine, but not methylatropine, antagonize both oxytocin- and ACTH-induced penile erection and yawning, suggesting that the oxytocin effect, as well as that of ACTH-MSH peptides involves activation of cholinergic transmission in brain, and that activation of the opioid system has an inhibitory action on oxytocin as well as on ACTH responses. However, the failure of naloxone to modify oxytocin response is against the idea that opioids exert a tonic inhibitory control on yawning and penile erection.

Excessive grooming is another behaviour that is associated with yawning and penile erection induced by ACTH-MSH peptides, and that seems to be mediated by an activation of central dopaminergic transmission. Recently icv oxytocin has been found to be capable of potentiating novelty-induced grooming behavioour, although less potently than ACTH and a-MSH, and in doses higher than those we have shown to induce yawning and penile erection. Whether grooming, yawning and penile erection induced by oxytocin are mediated same mechanism is unknown at present. However the prevention of oxytocin-induced excessive grooming, but not of yawning and penile erectin by low doses of haloperidol suggests that the two symptomatologies might be mediated by different mechanisms.

In conclusion, oxytocin is the most potent agent so far discovered to produce penile erection and yawning. In particular, the oxytocin effect on penile erection correlates well with previous studies showing that erotic stimuli, such as manipulation of the breast and genitalia, that usuall occur during the precoital phase of the sexual intercourse, are among the most potent inducers of oxytocin release from the neurohypophysis. Although the mechanism and site(s) of action of peptide are still unknown, the powerful effect of oxytocin suggests that endogenous brain oxytocin is implicated in the control of penile erection, and that abnormalities in its activity might be responsible for erection disturbances.