Yawning
behavior in male rats is associated with
decreases in in vivo DOPAC efflux from the
caudate nucleus.
Laping NJ, Ramirez VD.
Department of Physiology and
Biophysiology, University of Illinois, Urbana
-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.
Abstract
Young adult male rats were implanted with a
push-pull cannula aimed at the dorsal and
rostral areas of the caudate nucleus. Perfusate
samples were collected at two-minute intervals
for approximately one hour and assayed for DOPAC
concentrations. Simultaneously, yawning, penile
erections and grooming behavior were recorded.
Yawns were induced by systemic prolactin or
apomorphine injections. While mean DOPAC efflux
was elevated following prolactin (PRL) and
apomorphine decreased mean DOPAC efflux as
expected, yawns and penile erections induced by
both compounds were associated with rapid
momentary decreases in DOPAC efflux in these
living animals. Although yawning was associated
with significant decreases in DOPAC output, not
every momentary DOPAC decrease was associated
with a yawn, suggesting that the 'yawning
generator' most likely requires additional
inputs for the expression of a yawn.
INTRODUCTION
Yawning is a curious and still little
understood behavior which is displayed in many
vertebrate species. At least in humans it has
been shown that neither oxygen nor carbon
dioxide levels contribute to yawning rates.
While the physiologic importance of yawning
behavior is still not clear, it is nonetheless a
discrete and easily quantifiable behavioral
event that can be used as a model for
understanding how various CNS structures
interact to initiate and execute a behavior.
Current models based on pharmacological
experiments suggest that cholinergic systems, of
which a subset is under dopaminergic inhibitory
control, stimulate yawning. This is evident by
the findings that yawning is induced by
cholinomimetics as well as by low doses of
dopamine (DA) agonists or DA agents which
preferentially bind to DA autoreceptors and thus
reduce DA transmission.
Further support for this model are findings
that muscarinic antagonists block yawning
induced by both classes of compounds. Previous
studies including work in our own laboratory
have revealed that low doses of the DA receptor
agonist, apomorphine (APO), as well as low doses
of the pituitary hormone prolactin (PRL), can
induce yawning in young adult male rats. Both
compounds induce yawning in a dose-dependent
bell-shaped manner. Systemic administration of
either agent at relatively low doses (50 #g/kg
APO, 0.25 ~tg/kg PRL) induces yawning, whereas
higher and much lower doses do not. A
potentially important CNS site where APO and PRL
can act to induce this behavior in the caudate
nucleus (CN) since lesion studies of the
nigrostriatal DA system, as well as local
injections of APO or PRL into the CN, have
profound effects on yawning behavior.
Specifically, 6-hydroxydopamine (6-OHDA) lesions
of the substantia nigra or the CN greatly reduce
APO- and PRL-induced yawning, while local
infusions of APO or PRL into the CN evoke
yawning behavior. It should be noted, however,
that yawning can also be induced by local
injections of APO into the septum and the
paraventricular nucleus, suggesting that in vivo
DA activity in these areas may also be related
to the display of yawning behavior.
In order to examine the relationship between
this discrete behavioral event and rapid changes
in dopaminergic activity, we have utilized a
push-pull perfusion technique in which we
collect samples at two-minute intervals with
minimal perfusion artifacts. Since low
extracellular concentrations of DA preclude
consistent determination of in vivo DA release
under these conditions, in the present
experiments we examined
3,4-dihydroxyphenylacetic acid (DOPAC) output,
as an index of DA metabolism. It has been shown
that 80% of DA released is converted to DOPAC.
Also, within our own laboratory several studies
have indicated that with the push-pull perfusion
technique, DOPAC effiux is a good indicator of
DA release under normal physiological
conditions, though under pharmacological
conditions this may not be the case. The purpose
of this study was to focus on the CN and examine
the relationship between yawning behavior and
the in vivo release of DOPAC from the CN of
young adult male rats following low systemic
injections of APO or PRL.
DISCUSSION
These experiments have demonstrated that
yawning behavior and penile erections but not
grooming behavior are associated with negative
changes in DOPAC effiux in male rats injected
with PRL or APO. While yawning can occur when
mean levels of DOPAC output are high or low, the
data analysis in terms of rapid changes in DOPAC
efflux have shown that yawning events are
associated with momentary decreases in DOPAC
efflux. Interestingly, penile erections and
DOPAC effiux changes follow the same pattern in
animals receiving either PRL or APO. This is not
entirely surprising as it has been shown that
the same agents that induce yawning can induce
penile erections as well, and the frequency of
yawns has been positively correlated with the
frequency of penile erections 15. Additional
evidence for this relationship are the agonistic
effects of testosterone and antagonistic effects
of estrogen on yawning behavior. Perhaps the
same CNS structures that are involved in yawning
are also important in this particular aspect of
male sexual function.
It should be noted that the use of DOPAC as
an index of dopaminergic activity needs to be
taken cautiously since DOPAC efflux is a
function of both DA release, re-uptake and
monoamine oxidase activity and under certain
pharmacological conditions in vivo DA and DOPAC
release rates, as determined by microdialysis,
do not follow the same trends 36. However,
similar responses between DA and DOPAC were
observed following treatment with APO, or a
specific D2 agonist, or via cholinergic
stimulation. Moreover, since 80% of DA released
is converted to DOPAC and we have previously
observed that under push-pull perfusion
conditions of stimulated DA release DOPAC
release closely follows changes in DA output, we
assume that determinations of DOPAC release
under the present experimental conditions
provide an index of increases or decreases in
dopaminergic activity. While we are concerned
whether DOPAC is truly an index of DA release,
the interpretation of these results support the
hypothesis generated by pharmacological
experiments. The hypothesis that momentary
lifting of dopaminergic inhibition of
cholinergic neurons can induce yawning, is
consistent with these results if DOPAC is an
index of DA release.
However, arguments have been made that DOPAC
decreases reflect increases in DA activity. This
would indicate that yawning behavior requires DA
release for its activation. Most evidence
indicates that cholinergic activation is
required for yawning behavior; it is then
required that DA stimulate acetylcholine
release. There is some evidence that this might
be the case in some areas of the CN. The
viability of either hypothesis will be shown
when DA itself can be measured under this
experimental paradigm. At any rate the negative
decreases in DOPAC output were significant only
when penile erections or yawns occur, regardless
of the compound used to induce yawning behavior.
Moreover, increased DOPAC output was only
observed concomitant with grooming behavior.
This also supports findings that grooming
behavior is activated by DA activation.
Not every decrease in DOPAC efflux from the
CN resulted in a yawn or a penile erection. This
indicates that these behaviors require inputs
from additional neuronal systems for their
expression. The site or sites of integration for
these behaviors most likely compute these
additional signals with the information from the
CN when activation of the yawning sequence is
appropriate. Other CNS sites that are most
likely required are the paraventricular nucleus
of the hypothalamus and possibly the septum.
For, not only do chemical lesions of the
nigrostriatal DA system eliminate PRL- and
APO-induced yawning, but lesions of the
paraventricular nucleus block APOand
oxytocin-induced yawning as well~. In addition,
local infusions of APO into the septum induce
yawning. It would be interesting to discover the
common pathway or site to which these nuclei
project in the yawning sequence. Of importance
is the observation that PRLinduced yawns occur
when the mean DOPAC levels were higher than
preinjection levels, while APO-induced yawns
occur when the mean DOPAC levels were
significantly lower than preinjection levels.
Regardless, the yawning events under both
conditions occurred during momentary but clear
decreases in DOPAC efflux. The differences in
mean DOPAC levels and latencies at which these
behaviors occurred suggest different mechanisms
for APO- and PRL-induced yawns. The APO effect
is more easily explained by the activation of DA
autoreceptors which can decrease DA release and
synthesis and thus affect DOPAC efflux. This
decrease in DA transmission would lift the
inhibitory tonus on the cholinergic neurons and
in this way increase the probability that a yawn
occurs. PRL on the other hand has been shown to
increase DA release. In the present experiments
PRLinduced yawns occurred during heightened
DOPAC levels, probably reflecting higher DA
release rate. It has been shown that a
population of cholinergic neurons exist in the
dorsal region of the CN that can be stimulated
by DA. Therefore, it is reasonable to postulate
that activation of DA terminals controlling this
sub-population of cholinergic neurons could
occur following low doses of PRL.
