Penile erection and yawning are two
different behavioural patterns that often occur
concomitantly under physiological and
experimental conditions (see Holmgren et al.
1985). Penile erection is one of the most
important sexual responses in mammals, including
man, its achievement being essential for the
success of reproduction. However, this sexual
response can be observed not only during sexual
interaction but also in other contexts, such as
after simple manipulation of the genitalia or
during sleep and erotic fantasies in humans.
Depending on the particular context in which
penile erection occurs, different neural and/or
endocrine mechanisms may participate in its
regulation. As to the physiological significance
of yawning, it is pertinent to recall that
yawning is considered to have a role in
increasing attention when sleep is pressing in
dangerous situations or social circumstances
(for a review on the physiological significance
of yawning see Bertolini and Gessa 1981).
Among the various agents able to induce both
penile erection and yawning, oxytocin injected
into a lateral ventricle (ICV) of the rat is
certainly one of the most potent discovered so
far (Argiolas et al. 1986). Oxytocin effects are
thought to be mediated by a direct action of the
peptide on the hypothalamic paraventricular
nucleus (PVN). Accordingly, the PVN has been
found to be the most sensitive brain area for
the induction of these behavioural responses by
oxytocin (Melis et al. 1986), and electrolytic
lesions of this nucleus caused a marked decrease
in the number of yawning and penile erection
episodes induced by oxytocin (Argiolas et al.
1987b). In male rats yawning and penile erection
can also be induced by the systemic
administration of low doses of dopamine (DA)
agonists (see Serra et al. 1983) and by the ICV
injection of adrenocorticotropin (ACTH) and
related peptides (see Bertolini and Gessa 1981).
Recent experimental evidence from our laboratory
suggested that 1) DA agonists induce yawning and
penile erection by releasing oxytocin in the
central nervous system, possibly in the PVN
(Argiolas et al. 1987b, c; Melis et al. 1987);
2) DA agonists do not induce their effect by
releasing an ACTH-derived peptide in the
hypothalamus (Argiolas et al. 1987 a), and 3)
the hypophysis is necessary for the induction of
yawning and penile erection by DA agonists and
ACTH-derived peptides (Serra et al. 1983, 1987).
In order to verify if oxytocin induced the above
behavioural responses by releasing an
ACTH-derived peptide in the hypothalamus, and if
the pituitary is necessary for the expression of
yawning and penile erection induced by oxytocin,
we have studied the effect of ICV injection of
oxytocin on yawning and 'penile erection in
hypophysectomized rats and in rats neonatally
treated with monosodium glutamate (MSG), a
treatment that induces almost complete depletion
of ACTH-like peptides in the hypothalamus (Eskay
et al. 1979; Krieger et al. 1979). (...)
Discussion
The present results confirm and extend
previous findings from our laboratory showing
that ICV oxytocin induces penile erection and
yawning with a bell-shaped U-inverted
dose-response curve. The reason for such a
dose-response curve is unknown at present,
although similar dose-response curves have been
reported for other behavioral effects of
oxytocin (Bohus et al. 1978; Kovacs et al.
1985). A possible explanation for the
ineffectiveness of high doses of oxytocin is
that the peptide stimulates brain areas other
than those responsible for the appearance of
penile erection and yawning, which have an
inhibitory effect on the above responses. In
agreement with this hypothesis, no bellshaped
dose-response curve was observed when increasing
doses of oxytocin were injected into the PVN
(Argiolas et al. 1988a).
Moreover, the present results show that
hypophysectomy prevents the oxytocin effect.
Although the prevention was not complete,
suggesting that central mechanisms mediating
penile erection and yawning are still operative,
this finding is in line with previous
observations showing that intact pituitary
function is critical for the induction of the
above behavioural responses by oxytocin and
other agents as well. Indeed, hypophysectomy has
been found to strongly reduce penile erection
and yawning induced by either the DA-agonist
apomorphine (see Serra et al. 1983) or ACTH 1-24
(Serra et al. 1987). Moreover, the testosterone
reversal of the effect of hypophysectomy on
penile erection suggests that this hormone,
released from the testis by the pituitary
luteinizing hormone (LH), also has a permissive
role in the expression of this behavioural
response. This is in agreement with previous
findings showing that testosterone reverses the
inhibitory effects of castration on sexual
behaviour (for a review see Sachs and Meisel
1988), including the prevention of ACTH-induced
penile erection (Bertolini and Gessa 1981). It
is likely that the partial effect of
testosterone reflects that hypophysectomy
effects are more dramatic than those of
castration, and that more complete replacement
therapy with other pituitary and endocrine
hormones in addition to testosterone might be
much more effective in this case (see Eaves et
al. 1985). On the other hand, the lack of effect
of testosterone on yawning indicates that the
mechanisms mediating penile erection and yawning
can be dissociable, although common mechanisms
may participate in their concomitant occurrence
under certain physiological or experimental
conditions (see Hoimgren et al. 1985). All
together, the above findings suggest that the
pituitary gland and its target tissues (gonads,
adrenals, thyroid) have a permissive (perhaps
even synergistic) role in the expression of the
above behavioural responses induced by oxytocin,
ACTH and apomorphine. The pituitary and
pituitary-controlled glands might control the
above responses directly (i.e., by means of
pituitary or endocrine hormones which act
directly on the central nervous system) or
indirectly (i.e., by means of pituitary hormones
which control the release of endocrine hormones
by target tissues or by means of endocrine
hormones which modulate the activity of
pituitary hormones). The mechanism by which such
control occurs is not known and only speculation
is possible at present. One possibility is that
pituitary and/or endocrine hormones influence
the interaction of oxytocin and other
pharmacological agents with their receptors
and/or alter the response that usually follows
the drugreceptor interaction.
In contrast, the depletion of ACTH-MSH-like
peptides by neonatal MSG treatment was
completely ineffective in modifying
oxytocin-induced penile erection and yawning.
Although it is possible that hypothalamic
ACTH-MSH peptides remaining after MSG can still
be released in amounts sufficient to mediate
oxytocin effect by the surviving
opiomelanotropinergic neurons, perhaps becoming
superactive to overcome the lesion damage, this
finding suggests that oxytocin does not induce
the above responses by releasing an
ACTH-MSH-like peptide in the hypothalamus. This
is in agreement with previous findings from our
laboratory showing that ACTH and derived
peptides induce their effect by acting at sites
located downstream to DA or oxytocin receptors
or by a different mechanism, not involving DA or
oxytocin. Indeed, unlike oxytocin- and
apomorphine-induced response, ACTH-induced
penile erection and yawning are not antagonized
by the potent oxytocin antagonist
d(CH2)5Tyr(Me)-Orn8-vasotocin (Argiolas et al.
1987c), nor by electrolytic lesion of the
hypothalamic PVN (Argiolas et al. 1987b).
Conversely, it is unlikely that oxytocin induces
the above responses by releasing an ACTH-derived
peptide in extrahypothalamic brain areas not
affected by MSG treatment, since the
hypothalamus was found to be the most sensitive
brain area for the induction of yawning and
penile erection by ACTH (Bertolini and Gessa
1981).
As to the relationship between
oxytocin-induced penile erection and the
physiology of penile erection and sexual
behavior, the copulatory movements often
followed by ejaculation induced by oxytocin
suggest that the peptide activates neuronal
pathways controlling the spinal cord which in
turn regulates these penile and pelvic actions
(for a review on this subject see Sachs and
Meisel 1988). Accordingly, electrolytic lesion
of the PVN caused almost complete depletion of
oxytocin in brain and spinal cord (Lang et al.
1983), and abolished penile erection induced by
oxytocin (Argiolas et al. 1987b). While our
findings suggest that brain oxytocin is implied
in the control of penile erection, other
experimental evidence suggests that this effect
of oxytocin may also occur in the regulation of
sexual behavior. Accordingly, the ICV injection
of a potent oxytocin antagonist,
d(CH2)5Tyr(Me)-Orn8-vasotocin, inhibits male
copulatory behavior in rats (Argiolas et al.
1988 b). In particular, this oxytocin analog
influences all the parameters of copulatory
behavior, the intromission and ejaculation
latencies and the mount, intromission and
ejaculation frequencies as well. In view of the
ability of the oxytocin antagonist to prevent
penile erection induced by oxytocin (Argiolas et
al. 1987e), it is likely that the blockade of
central oxytocm receptors induces an inability
of the animals to achieve penile erection, which
in turn causes a decrease in the intromission
frequency and the abolition of ejaculation. The
above findings correlate well with previous
findings showing that 1) circulating levels of
oxytocin are increased immediately after
ejaculation in rabbits (Stoneham et al. 1985)
and in the human sexual response (Carmichael et
al. 1987), 2) ICV oxytocin has been found to
increase lordosis behavior in female rats
(Arletti and Bertolini 1985), and 3) oxytocm
improves sexual performance of vigorous sexually
experienced male rats in the presence of a
female in oestrus, as indicated by the decrease
in the post-ejaculatory interval observed in
oxytocin-treated rats (Arletti et al. 1985).
However, other studies have reported that
oxytocin increases the post-ejaculatory
interval, suggesting a specific role of the
peptide in the control of this parameter of the
copulatory behavior (Stoneham et al. 1985). This
discrepancy might be due to the different doses
of oxytocin used in the above studies (1 ng
versus doses higher than 60 ng). More complete
dose-response curves might clarify this point
and perhaps reveal that oxytocin has a dual
effect on the post-ejaculatory interval.
In conclusion, oxytocin apparently does not
induce penile erection and yawning by releasing
an ACTH-related peptide from
opiomelanotropinergic neurons. Moreover, as for
DA agonists and ACTH-derived peptides, intact
pituitary function is necessary for the
expression of these oxytocin induced behavioral
responses.
