Penile erection and yawning are two
different behavioral patterns that often occur
concomitantly under physiological and
experimental conditions. While the importance of
penile erection in reproduction of mammals does
not need to be stressed, it is pertinent to
recall that yawning, alone or associated with
stretching, is considered an ancestral vestige
surviving throughout evolution that subserves
the purpose of arousal.
Several lines of experimental evidence
suggest that a central dopamine-oxytocin link
plays a key role in the expression of such
symptomatology. Accordingly, both apomorphine
and oxytocin induce penile erection and yawning
when unilaterally injected in the
paraventricular nucleus (PVN) of the
hypothalamus; lesions of the PVN abolish
apomorphine and oxytocin responses; dopamine
receptor blockers prevent apomorphine but not
oxytocin effects; nonapeptide oxytocin
antagonists prevent apomorphineinduced penile
erection and yawning; finally, apomorphine
increases oxytocin content in brain, as well as
in plasma.
The above results support the hypothesis
that apomorphine and dopaminergic agonists
induce penile erection and yawning by releasing
oxytocin in the CNS by acting in the PVN. In
this regard, it is pertinent to recall that the
PVN contains not only the majority of the cell
bodies of those oxytocinergic neurons, which
project to extrahypothalamic brain areas, that
is, septum, hippocampus, olfactory bulb, brain
stem, pons, medulla and spinal cord, but also
dopaminergic neurons, located in the proximity
of oxytocinergic cell bodies, that belong to the
incertohypothalamic dopaminergic system.
Recently, it has been shown that
septohippocampal lesions prevent
apomorphine-induced penile erection and yawning.
Taken together with the finding showing that
oxytocin induces penile erection and yawning
when bilaterally injected into the CA1 field of
the hippocampus, this raises the possibility
that the oxytocinergic pathways activated by
apomorphine and that mediate penile erection and
yawning are those projecting to the septum and
hippocampus.To verify such a hypothesis, we
studied:
the effect of a potent oxytocin nonapeptide
antagonist injected into the PVN on apomorphine-
and oxytocin-induced penile erection and
yawning;
the effect of oxytocin and apomorphine
microinjected in the medial septum (NIS) on
these behavioral responses;
the effect of electrolytic lesions of the MS
on oxytocin-induced penile erection and yawning,
as well as on oxytocin concentration in the
hippocampus.
The present study shows that the oxytocin
antagonist Orn-vasotocin injected in the PVN
prevents penile erection and yawning induced by
oxytocin but not by apomorphine, while MS
lesions that decrease hippocampal oxytocin
concentration prevent the above behavioral
responses induced by apomorphine but not
oxytocin. These results extend previous findings
suggesting that the dopaminergic agonist
apomorphine induces penile erection and yawning
by releasing oxytocin in the CNS.
In particular, the failure of
d(CH2),Tyr(Me)-Orn8-vasotocin to prevent
apomorphine response when injected in the PVN,
in spite of its efficacy when given ICV,
suggests that apomorphine induces penile
erection and yawning by increasing oxytocinergic
activity by acting directly on dopaminergic
receptors at the level of the oxytocinergic cell
bodies or indirectly by removing some inhibitory
input on oxytocinergic neurons, rather than by
releasing oxytocin in the PVN. On the other
hand, the ability of
d(CH2)5Tyr(Me)-Orn8-vasotocin injected into the
PVN to prevent ICV or PVN oxytocin response
confirms that oxytocin acts mainly in the PVN to
induce penile erection and yawning possibly by
stimulating specific oxytocinergic receptors
located in this hypothalamic nucleus.
In line with the hypothesis that apomorphine
induces penile erection and yawning by
activating oxytocinergic neurons, it is likely
that oxytocin also induces the above responses
by increasing its own transmission, perhaps by
stimulating oxytocinergic receptors located in
the cell bodies of its own neurons in the PVN.
Accordingly, exogenous oxytocin injected in the
PVN has been found capable of activating its own
release in vivo and in vitro from magnocellular
neurons, and immunoreactive oxytocinergic
synapses have been found to impinge on the cell
bodies of oxytocinergic neurons in both
hypothalamic supraoptic and paraventricular
nuclei.
In agreement with the above hypotheses, the
failure of apomorphine to induce penile erection
and yawning when injected directly in the MS or
in the hippocampus or in MS-lesioned rats,
although effective when injected in the PVN,
suggests that apomorphine induces the above
responses by activating those oxytocinergic
pathways originating in the PVN that reach the
medial septum or the rostral hippocampus (tenia
tectae) passing rostrally to the septum. The
second possibility is the most likely, being
favored by the failure of oxytocin to induce
penile erection and yawning when injected in the
MS, by the finding showing that MS lesions
decrease hippocampal oxytocin concentration only
in those animals found unresponsive to
apomorphine and by the failure of
iontophoretically applied oxytocin to activate
MS neurons.
The ineffectiveness of apomorphine to induce
penile erection and yawning when injected into
the MS is in contrast with previous studies
showing that the bilateral injection of
apomorphine into the lateral septum induces
yawning. The discrepancy might be explained by
the fact that in those studies doses of
apomorphine (10 jug and higher per site) were
used that were too high and probably resulted in
the spread of the drug to the active site.
Accordingly, it is unlikely that apomorphine
acts directly in the MS, although a
septohippocampal dopamine-acetylcholine link has
been supposed to be involved in the expression
of yawning and pende erection. In fact, if the
latter hypothesis were correct, the stimulation
of dopaminergic receptors in the MS would induce
a cholinergic inhibition mediating in turn pende
erection and yawning. Against such hypothesis,
muscarinic agonists induce the above behavioral
responses, possibly acting in the hippocampus,
and blockade of cholinergic transmission by
muscarinic antagonists atropine and scopolamine,
as well as by MS lesions, which decrease
hippocampal acetylcholine content, prevent
apomorphine response.
Taken together with the inability of MS
lesion to prevent oxytocin response, the above
results suggest that apomorphine induces
penile erection and yawning by activating
selectively the hypothalamic-hippocampal
oxytocinergic projection. In this respect,
it is noteworthy that the hippocampus plays a
key role in the expression of penile erection
and sexual behavior, apomorphine increases
oxytocin content in this brain area at doses
that induce penile erection and yawning,
oxytocin induces these behavioral responses when
injected in the CA1 field of the hippocampus,
and oxytocin excites hippocampal neurons by
acting on uterine-type oxytocinergic receptors,
those that mediate penile erection and yawning.
Nevertheless, it is likely that this
hypothalamic-hippocampal oxytocinergic pathway
plays only a minor role or is not involved at
all in the oxytocin response. In fact, the
inability of MS lesion to prevent the effect of
oxytocin injected in the PVN raises the
possibility that oxytocin may act in the PVN to
induce penile erection and yawning by
stimulating other neuronal pathways not
involving the hippocampus, that is, the
oxytocinergic projections reaching the pons,
medulla, and spinal cord. Accordingly, the
PVN is considered a sort of integration center
between the central and autonomic nervous
systems. In view of the prevention of
oxytocin effect by PVN lesions but not by MS
lesions, it is tempting to speculate that a
hippocampal-hypothalamic pathway, whose activity
is modified by apomorphine treatment, mediates
in turn the activity of the same neuronal
circuits modified by PVN oxytocin and
controlling the above behavioral responses. In
agreement with this hypothesis, neuronal
pathways originating in the hippocampus and
septum that exert an excitatory input on
vasopressinergic and oxytocinergic neurons in
the PVN have been described.
The involvement of oxytocin in different
central neuronal pathways that control penile
erection and yawning deserves some
comment.
One of these pathways, that is, the
hypothalamic-hippocampal oxytocinergic pathway,
is activated by apomorphine and probably by
other dopaminergic agonists through the
stimulation of D, dopamine receptors in the PVN.
Interestingly, the PVN contains the A14 group of
the so-called incertohypothalamic dopaminergic
system. These small dopaminergic neurons
arborize extensively and surround the
oxytocinergic neuronal cell bodies in the PVN.
This suggests that this still poorly
characterized hypothalamic dopaminergic system
plays a major role in the expression of yawning
and penile erection.
Since the hypothalamus, the first
developed brain structure from a phylogenetic
point of view, plays a primary role survived
during evolution from fishes to primates in
reproduction, it is easy to speculate that
hypothalamic oxytocin is involved in the control
of penile erection in mammals. The involvement
of oxytocin in the expression of penile erection
in brain areas phylogenctically developed later,
but strictly connected to the hypothalamus (ie.,
the limbic system), might be one of those
mechanisms by means of which high brain centers
control such a primary sexual function. In
particular, the activation of central
oxytocinergic pathways by dopamine, a
neurotransmitter involved in motivation and
rewarding mechanisms, raises the possibility
that oxytocin in the limbic system plays a role
in sexual arousal and motivation (libido in
men), while its action in the hypothalamus may
be related mainly to erectile and ejaculatory
performance (potency in men).
