Monosodium
glutamate does not alter ACTH- or
apomorphine-induced penile erection and
yawning
A Argiolas, MR Melis, W Fratta, A Mauri, GL
Gessa
Institute of Pharmacology,
University of Cagliari, Italy
The intracerebroventricular (ICV) injection
of adrenocorticotropin (ACTH), alpha-melanocyte
stimulating hormone (aMSH) and derived peptides,
induces excessive grooming, yawning, stretching
and penile erection in rats. While grooming
occurs already at doses of 0. 1 nmol of ACTH or
a-MSH, doses higher than 1-2 nmol are needed for
inducing the latter effects. While the
importance of penile erection in reproduction
does not need to be further stressed, the other
behaviours are important as indicators of
arousal. In particular, grooming is believed to
have a deactivating role in restoring
behavioural homeostasis, while yawning, and
stretching are believed to have the role of
increasing attention when sleep is pressing
in front of a danger or social circumstances.
The above behavioural responses are thought to
be mediated by a direct action of ACTH-MSH
peptides in the hypothalamus, since this brain
area has been found the most sensitive for the
induction of the above effects by ACTH 1-24.
Accordingly, recent studies have demonstrated
the existence of neurons in the central nervous
system containing proopiomelanocortin, the 31 kD
protein precursor of ACTH, a-MSH and
beta-endorphin. These neurons originate in the
arcuate nucleus of the hypothalamus and send
their projections to this and other brain
regions.
Yawning and penile erection can be induced
in rats also by the systemic adminstration of
low doses of dopamine (DA) agonists other than
by ACTH-MSH peptides. It has been suggested that
DA agonists may induce such responses by
releasing an ACTH-derived peptide from the
pituitary gland. Recently, it has been
discovered that the neonatal administration of
monosodium glutamate (MSG) induces the almost
complete depletion of ACTH, a-MSH and
b-endorphin in the rat hypothalamus, providing a
useful model to study the function of these
peptides in brain. It has been also shown that
hypophysectomy, that eliminates circulating
ACTH, a-MSH and b-endorphin without altering
their concentration in the hypothalamus, reduces
penile erection and yawning induced not only by
apomorphine, but also by ACTH 1-24. Two main
conclusions derive from the above findings:
(1) an intact pituitary function is needed
for the expression of the above responses of
both ACTH and apomorphine, and
(2) apomorphine apparently does not induce
penile erection and yawning by releasing an
ACTHderived peptide from the pituitary
gland.
However, the possibility remains that
apomorphine induces yawning and penile erection
by releasing an ACTH-derived peptide from
central opiomelanotropinergic neurons. In an
attempt to clarify the role of hypothalamic
ACTH-MSH peptides in the expression of penile
erection and yawning, we have studied the effect
of ACTH 1-24 and apomorphine on the above
responses in neonatally MSG-treated rats.
[...]
DISCUSSION
The present results show that the depletion
of hypothalamic ACTH and a-MSH by neonatal MSG
treatment does not modify yawning and penile
erection induced by ICV ACTH 1-24 or by low
doses of systemic apomorphine. The reduced
growth of MSG-treated rats, that is secondary to
the destruction of hypothalamic growth hormone
releasing hormone, seems not to be important for
the expression of ACTH- and apomorphine-induced
responses. In contrast, penile erection and
yawning induced either by ACTH 1-24 or by
apomorphine, were prevented by hypophysectomy,
in agreement with previous studies. Taken
together, the prevention of ACTH-induced yawning
and penile erection by hypophysectomy and the
ineffectiveness of hypothalamic ACTH-MSH
depletion by MSG to alter ACTH-induced effect,
indicate that an intact pituitary function
rather than the integrity of hypothalamic
ACTH-MSH-containing neurons, is important for
the induction of yawning and penile erection by
ACTH-MSH peptides. As previously discussed, this
suggests that the pituitary gland exerts a
permissive role in the expression of ACTH- and
apomorphine-induced penile erection and yawning.
In agreement with this hypothesis,
hypophysectomy has been found to cause a marked
decrease in central behavioural effects induced
by other neuropeptides, and this decrease was
completely prevented by the combined
administration of testosterone, corticosterone
and growth hormone.
On the other hand, previous studies have
shown that hypophysectomy does not modify
excessive grooming induced by ACTH, indicating
that such responses might be mediated by a
different mechanism. However, the above studies
were performed in 5 days hypophysectomized rats,
while one month hypophysectomized rats were used
in the present study. Therefore, it is possible
that the failure of hypophysectorny to mqdify
ACTH-induced grooming was due to the short
post-operative period used in the previous
study.
The failure of hypothalamic ACTH-MSH
depletion to modify ACTH-induced yawning and
penile erection is surprising. Indeed, if
yawning, stretching and penile erection after
ICV ACTH are really due to the stimulation of
brain ACTH-MSH receptors, one would expect a
compensatory increase in the sensitivity of
these receptors, but this was not observed. In
agreement with the present study, neonatal MSG
treatment was found to be unable to modify
excessive grooming induced by ACTH and to induce
significant changes in opiate receptors.
Moreover, an attenuated analgesic response to
morphine and a significant reduction in the
stress-induced prolactin release have been shown
in MSG-treated rats. However, these changes
suggest a decreased rather than an increased
sensitivity to opiates and ACTH-MSH
peptides.
The inability of neonatal MSG treatment to
modify apomorphine-induced penile erection and
yawning suggests that apomorphine and other
DA-agonists do not induce such responses by
releasing an ACTH-derived peptide from central
ACTH-MSH containing neurons. Thus, although both
apomorphine and ACTH-derived peptides induce
penile erection and yawning, it is possible that
they act by a different mechanism or at
different steps in the neuronal circuitry
involved in the expression of these responses.
If really apomorphine and ACTH act one after the
other to induce yawning and penile erection, it
is likely that the site of action of
ACTH-derived peptides is situated after that of
apomorphine, since ACTH-induced response is not
antagonized by doses of neuroleptic drugs that
completely prevent apomorphine-induced
response.
Recently, we have found that the ICV
injection of nanogram amounts of oxytocin
induces penile erection and yawning in male
rats. The powerful effect of oxytocin in
eliciting the above responses, together with the
presence of this neuropeptide in brain neurons
in addition to the posterior pituitary, raises
the possibility that apomorphine and/or
ACTH-derived peptides induce penile erection and
yawning by releasing oxytocin in some brain area
or vice versa. The failure of neonatal MSG
treatment to modify significantly the
hypothalamic concentration of oxytocin leads us
to speculate that apomorphine induces penile
erection and yawning by releasing oxytocin in
brain. Accordingly, both penile erection and
yawning induced by oxytocin or apomorphine, but
not by ACTH 1-24, have been found to be
prevented by the ICV injection of the oxytocin
antagonist d(CHA, Tyr-(Me)-Oml vasotocin.
In conclusion, although the possibility that
ACTH-MSH peptides induce the above responses by
acting in some extrahypothalamic brain area
where they are not depleted by neonatal MSG
treatment cannot by completely ruled out, the
depletion of hypothalamic ACTH and a-MSH does
not alter penile erection and yawning induced by
ACTH 1-24 and apomorphine.
