Discussion :
We have shown that oPRL injected
subcutaneously in the neck induces yawning
and/or SYS in young adult male rats. A
bell-shaped dosedependant response characterized
this phenomenon with 0.25 lig/kg being the most
effective dose. In addition, the number of
yawns varies with the time of day. Both APO
and oPRL induced a significantly greater yawning
frequency at 1600 than at 1000 hr. Even though
both compounds induced an identical behavior the
latency of yawning was different. APO, at low
doses, at which it is thought to stimulate
autoreceptors, had a short latency, 12 min at
1000 hr, whereas PRL which increases DA release,
had a longer latency, 37 min at 1000 hr.
APO has been known to induce other
stereotyped behaviors. At high doses, greater
than 250 µg/kg, APO induces continuous
licking, sniffing, and chewing which is
sometimes accompanied by constant movement, and
at this dose APO is thought to stimulate DA
postsynaptic receptors. However, lower doses of
APO (50-100 gg/kg) induce yawning behavior and
it is thought that APO at these doses is acting
on the presynaptic autoreceptors, inhibiting DA
release, and causing an increase in the firing
of the cholinergic neurons in the corpus
striatum which are under inhibitory control by
the nigro striatal dopamine system. Furthermore
there is evidence that cholinomimetic drugs are
effective in evoking yawning. Thus the
conclusion is that the DA system inhibits the
-yawning generator- via inhibiting cholinergic
neurons.
However, there are other factors involved in
yawning. Protein hormones such as
adrenocorticotrophic hormone (ACTH),
melanocyte-stimulating hormone (MSH), and
lipotrophic hormone when injected
intracerebrally induce yawning in a variety of
mammals. Also when rats are hypophysectomized
the ability to yawn in response to APO is lost.
Presumably one or more hormones of the pituitary
are involved in yawning behavior. ACTH and MSH
have been shown to be important and now we have
demonstrated prolactin's effectiveness in
physiological doses. But if APO induces yawning
by acting on the DA autoreceptors and inhibiting
DA transmission, how does PRL induce yawning if
it is said to facilitate DA transmission ?
After initial stimulation PRL could cause a
secondary inhibition of the nigrostriatal
dopamine system.Groves showed that infusing the
caudate putamen with amphetamine (which
facilitates DA transmission) resulted in a
decrease of the firing rate of the substantia
nigra after a time lag of approximately 30 min.
This latency follows our own finding that PRL
will induce yawning behavior after a mean
laiency of 37 min. There is evidence of DA
stores in the dendrites of the dopaminergic
neurons of the substantia nigra. Furthermore, it
bas been shown that if DA is applied to the
dendrites of these neurons they will then
decrease their firing rate. Thus there are at
least two possible ways in which PRL may cause
eventual inhibition of the DA system. First,
after PRL releases dopamine, this
neurotransmitter then binds to its presynaptic
autoreceptors and inhibits further DA release.
Secondly, PRL may release dopamine stored in the
dendrites of the dopaminergic cell bodies in the
substantia nigra which will bind to dendritic
autoreceptors and cause a decrease in the firing
rate of the DA neurons. This decrease of
doparninergic activity results in lifting of the
inhibitory control on the cholinergic neurons
which then will activate the yawning
behavior.
Since yawning behavior is influenced by
pituitary hormones it is reasonable to consider
that the cyclicity of pituitary hormone output
may change the responsivity of the -yawning
center.- Indeed, if we compare circadian levels
of PRL and ACTH with the spontaneous and
PRL-induced yawning during a circadian cycle one
finds that PRL and ACTH levels are high in the
late afternoon and night when the spontaneous
and PRL-induced yawning frequencies are also
high. Thus PRL and perhaps other pituitary
hormones by themselves or in a synergistic
fashion increase the sensitivity or responsivity
of the -yawning generator.- The physiological
relevance of PRL as well as other peptides
affects on yawning behavior remain to be
elucidated.
