The administration of ACTH or ACTH-derived
neuropeptides into the cerebrospinal fluid (CSF)
in mammals induces a behavioural syndrome
characterized by recurrent episodes of
stretching, yawning and penile erection.
A similar behavioural syndrome, though less
intense, may be induced by systemic
administration of minute doses of apomorphine or
other dopamine (DA) receptor agonists .
We have recently shown that inhibition of
protein synthesis or hypophysectomy prevents
apomorphine induced yawning and penile erection
and suggested that these behavioural responses
might be mediated by the release of ACTH or MSH
newly synthetized from pituitary, reaching the
brain via a retrograde portal flow. Further
support for this hypothesis is provided by the
finding that small doses of apomorphine
stimulate ACTH release from pituitary.
However, an alternative explanation for the
suppressant effect of hypophysectomy on yawning
and penile erection may be that hypophysectomy
modifies the sensitivity of receptors in the CNS
to DA and/or ACTH responsible for such
behaviours.
To clarify this hypothesis, we investigated
whether hypophysectomy would modify yawning and
penile erection induced by the administration of
ACTH 1-24 in rats.
The present results indicate that
hypophysectomy prevents ACTHI induced yawning
and penile erection, suggesting that
pituitary has a permissive role for the
expression of specific behaviours mediated by
ACTH and related neuropeptides.
[...]
Discussion
We found that the removal of pituitary,
besides preventing apomorphine-induced yawning
and penile erection, also antagonizes these
behavioral responses induced by ACTH suggest
that hypophysectomy modifies the sensitivity of
receptors to DA and ACTH in the brain mediating
yawning and penile erection.
The consequence of hypophysectomy seems to be
selective for specific receptors since it causes
the loss of apomorphine and ACTH ability in
inducing yawning and penile erection, but fails
to affect other behavioural responses to
apomorphine, such as the hypomotifity produced
by the minute doses of apomorphine, and motor
stimulation and stereotypy produced by high
doses of the drug (Serra et al., in
preparation). Moreover, de Wied's group has
shown that hypophysectomy docs not prevent the
positive effect of ACTH and ACTH-derived
peptides on memory and learning in rats,
suggesting that the central ACTH receptors
involved in such response are not modified by
hypophysectomy.
Pituitary might control the sensitivity of
central DA and ACTH receptors mediating yawning
and penile erection directly, via some pituitary
hormone, reaching the brain via retrograde
portal flow, or indirectly, via some
pituitarycontrolled hormone. Whereas
testosterone might have a permissive role in the
sexual effect of apomorphine and ACTH, the lack
of testosterone cannot account for the loss of
the yawning response since castration fails to
modify such effect elicited by ACTH or
apomorphine administration.
The present results are of great interest
because they suggest that pituitary has a
"trophic" action not only on peripheral target
organs but also on structures in brain
controfling specific behavioural responses.
These results leave unresolved.the problem of
whether yawning and penile erection induced by
apomorphine and other DA-agonists involve the
release of ACTH-derived neuropeptides from the
pituitary or from central peptidergic neurons.
The solution of this problem is hampered by the
fact that, unfortunately, no specific
antagonists for central receptors to ACTH and
ACTH-related peptides are presently available.
However we have observed that sulpiride, a
specific DA receptor blocker, potently
antagonizes apomorphine-induced yawning but
fails to affect this behavioural response induce
by ACTH, suggesting that ACTH-induced yawning
involves neither DA receptor activation nor DA
release.
