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.
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
