- 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.
|
