Prolactin-induced
yawning behavior requires an intact
nigro-striatal dopamine system
Laping NJ, Ramirez VD
Department of Physiology and
Biophysics, University of Illinois, Urbana,
Illinois
-Laping NJ,
Ramirez VD Prolactin-induced yawning
behavior requires an intact nigro-striatal
dopamine system Pharmacol Biochem Behav
1988;29(1):59-62
-Laping NJ,
Ramirez VD Prolactin induces yawning and the
stretching yawning syndrome in young adulte male
rats. Hormones & Behavior 1986;20:49-59
-Laping
NJ, Ramirez VD.Yawning behavior in male rats
is associated with decreases in in vivo DOPAC
efflux from the caudate nucleus. Behav Brain
Res. 1990;36(1-2):65-72.
YAWNING behavior, a discrete event with a
low spontaneous occurrence, appears to be a well
suited model to study behaviors linked to
dopaminergic systems such as the nigro-striatal
dopamine system. Yawning is also of clinical
interest since it has been reported that
psychotics rarely yawn, and yawning is
symptomatic in a wide range of central nervous
system disorders such as brain lesions, chorea,
and encephalitis. It has been shown that a
variety of substances, such as dopamine (DA)
agonists, cholinergic agonists, as well as
peptide hormones, induce yawning behavior.
A prevalent view of the regulation of
yawning considers that cholinergic neurons which
stimulate yawning are under inhibitory control
by dopaminergic neurons. Yawning evoked by
cholinomimetics, such as physostigmine or
pilocarpine, are thought to be mediated by
central muscarinic receptors, since yawning
induced in this manner is blocked by scopolamine
hydrobromide. Furthermore, it is known that the
striatal cholinergic system can be inhibited by
dopamine. In light of this, it is not surprising
that agents which inhibit central dopamine
systems induce yawning behavior as well. For
example, low doses of dopamine agonists, such as
apomorphine (APO) or piribedil
(which are thought to be preferentially
stimulate dopamine autoreceptors at low doses,
and thereby inhibit the dopamine system) can
induce yawning behavior as well as the stretch
yawning-syndrome. Interestingly, scopolamine
also blocks yawning, when induced with APO or
piribedil. In terms of dopaminergic agents,
yawning behavior is thought to be evoked by
compounds which activate dopamine autoreceptors,
as illustrated when autoreceptor-selective drugs
are used such as 3-PPP or TL-99.
However, yawning behavior is also induced by
protein hormones from the pituitary, such as
ACTH, oxytocin, and alpha MSH. We have shown
that low doses of ovine prolactin (PRL)
[0.25 1µg/kg] injected systemically
induce yawning in young adult male rats. In
spite of the initial release of dopamine by PRL
from the striatal terminals, we have
hypothesized that the initial release of
dopamine eventually will bind to dopamine
autoreceptors and then induce yawning behavior.
Since there was an indication that infusions of
prolactin into the caudate nucleus can induce
yawning as well, and that 6OH-Dopamine (6-OH-DA)
lesions of the striatum abolished APO induced
yawning in rats, it was of interest to
investigate if the nigro strital dopamine system
is involved in prolactin as well as Apo induced
yawning behavior. Herein , we report the effect
of bilatreal 6-OH-Da lesions of the substantia
nigra on physostigmine, apomporphine and
prolactin induced yawns. [...]
DISCUSSION
Our results indicate that
physostigmine-induced yawning is not reduced by
a bilateral lesion of the substantia nigra,
whereas both APO- and PRL-induced yawning
are. Physostigmine most likely mimics
cholinergic system involvement in yawning
stimulation. However, the present results show
that physostigmine does reduce DA concentrations
in the caudate nucleus in intact as well as
lesioned rats. This reduction may be due to
cholinergic activation of GABA, which can
inhibit dopamine neurons. In any event,
different sites of action appear to be
responsible for physostigmine-induced yawning
versus APO- and PRLinduced yawning.
Also in the intact animals, both DA and DOPAC
concentrations in the caudate nucleus were lower
in the APO-30' and PRL groups as compared to
those of saline controls, at times that were
temporally related te the yawning display. It
has been proposed that one site in the central
nervous system where APO and PRL act to induce
yawning behavior is the nigro-striatal dopamine
system. In support of this hypothesis is
evidence indicating that not only do infusions
of APO within the caudate nucleus decrease
striatal neuron firing rates, but that a local
infusion of APO is also capable of inducing
yawning. The concentrations of APO used in the
present experiment could act on the
nigro-striatal dopamine autoreceptors, given
that APO at these low doses binds
prefèrentially to dopamine autoreceptors.
Activation of these autoreceptors could inhibit
synthesis and/or decrease release of dopamine
thereby lifting dopaminergic inhibition of
cholinergie systems which have been demonstrated
to activate yawning.
With regard to PRL, intra-striatal but not
intraaccumbens infusions of PRL can induce
yawning (, unpublished observations). It is
proposed that PRL induces yawning by a similar
mechanism to that of APO. However, this
mechanism is probably secondary to its initial
releasing action of DA as indicated by the
longer latency of PRLinduced yawning. In this
way small doses of PRL can release small amounts
of DA from the caudate nucleus, and ultimately
decrease dopaminergic activity through
autoreceptors after a certain latency period. In
support of the temporal differences between APO-
and PRL-induced yawning is the finding that DA
and DOPAC concentrations had recovered by 60
minutes in the intact APO group but not in the
intact PRL group.
It can be speculated that in the lesioned
animals the remaining intact neurons must
increase their output to compensate for the loss
of functional dopamine neurons. This could be
accomplished in part by a decrease in dopamine
auto-receptors which leads to a decrease in
feedback inhibition and/or by an increase in
receptors at the postsynaptic site leading to
hypersensïtivity. The results of the APO30'
groups suggest that the number of functional
autoreceptors have decreased in the lesioned
condition because in this group the DA and DOPAC
concentrations were not significantly lower than
the lesioned saline controls. In the lesioned
APO-60' group the DA and DOPAC concentrations
were much higher than the lesioned saline
controls. A lesion of the nigro-striatal
dopamine system can induce postsynaptic
hypersensitivity, which was observed in these
experiments by the display of stereotyped
behavior in the majority of lesioned animals.
However, such hyperactivity could also be the
result of DA release from degenerating nerve
terminals as well as decreased DA reuptake. In
the lesioned condition low doses of APO may in
fact stimulate postsynaptic receptors. The
activation of postsynaptic receptors could
inhibit the GABA-ergic inhibitory feedback loop,
resulting in an increased impulse flow of the
nigro-striatal dopamine neurons. It has been
shown that the increased impulse flow of
dopaminergic neurons can result in an increase
in DA synthesis. Thus as it was the case one
could expect higher DA and DOPAC concentrations
60 minutes after the APO injection.
PRL releases DA and with the decreased number
of functional autoreceptors less effective
feedback inhibition would be observed. Again,
the transient release of dopamine caused by PRL
could have inhibited the GABA-ergic feedback
loops, resulting in increased impulse flow of
dopamine neurons. This could contribute to the
greater DA concentrations observed in the
lesioned PRL group compared to the lesioned
saline group. However, in this group no increase
in DOPAC concentration was observed.
In summary, physostigmine-induced yawning
does not require an intact nigro-striatal
dopamine system. In contrast, APO- and
PRL-induced yawning behavior requires an intact
nigro-striatal dopamine system. But, the
mechanism of action of these two substances
appear to be different. The findings that PRL in
addition to other pituitary hormones such as
ACTH, MSH, and oxytocin, can induce yawning
behavior, suggests that the nigro-striatal
dopamine system may be an important site where
pituitary hormones modulate behaviors.
-Sato F et
al. Suppressive effects of chronic
hyperprolactinemia on penile erection and
yawning following administration of apomorphine
to pituitary-transplanted rats Journal of
Anthology 1997; 18; 1; 21-25
