The mid-twentieth century reviews on
yawning by Heusner (1946) and Barbizet (1958 )
offered adequate coverage of earlier literature
on this ubiquitous and apparently trivial
behavioral pattern. Apart from a burgeoning of
research in the twenties on the physiological
mechanisms involved in yawning and on some
pathological conditions with which it might be
associated, specially by German authors this
field has continued to be rather neglected until
our day. Even if the mechanisms underlying
yawning are far from properly elucidated, and
its biological significance is largely ignored,
important advances in its understanding may be
anticipated, due to the increasing number of
research groups, especially among
neuropharmacologists, paying attention to this
motor act.
In 1955 Ferrari et al.were fortunate enough
to come upon a peculiar behavioral syndrome:
when dogs were intracerebroventricularly
injected with a commercial preparation of
adrenocorticotrophic hormone (ACTH), after a
latent period of about 30 min, the animals
started to yawn andstretch very frequently. This
was the first report on pharmacological
induction of yawning. Some years later, this
Italian group extended their observations to
other animal species and demonstrated that the
stretching-yawning syndrome (SYS) was elicitable
both by ACTH and melanocyte-stimulating hormone
(MSH). Since in these early experiments they
showed the antagonistic effects of atropine and
scopolamine on SYS, they suggested that a
cholinergic mechanism might be involved. More
than a decade later several authors demonstrated
that other neurotransmitter-related drugs also
had yawning-inducing effects and that most (if
not all) of them seemed to involve a cholinergic
mechanism, as judged by their susceptibility to
muscarinic blocking drugs.
In recent years it has been suggested that
elicitation of yawning is mainly the result of
an interaction, somewhere in the brain,
between inhibitory dopaminergic and
excitatory cholinergic influences on the
built-in motor program. for yawning. Yawning
elicited by low doses of apomorphine and other
dopamine (DA) agonists has most generally been
interpreted as the result of their selective
action on low-threshold DA autoreceptors
regulating impulse discharge, synthesis and
liberation of the neurotransmitter. Nevertheless
several authors have postulated that the
yawn-inducing effect of low doses of DA agonists
is a postsynaptic excitatory effect upon
exquisitively sensitive DA2 receptors. Higher
doses of DA agonists would decrease yawning by
acting directly on high-threshold postsynaptic
DA yawninhibitory receptors.
Moreover, there are several other
neurotransmitter and hormonal mechanisms known
to influence yawning, directly or indirectly .
Thus, a rather high number of proteins (enzymes,
receptors, etc.) may be involved in the
regulation of this behavioral pattern.
Therefore, it could be expected that some
differences in the level of spontaneous yawning
frequency might have a genetic background.
By inbreeding we have developed 2
Sprague-Dawley sublines: one of them yawns
spontaneously at a low frequency (LY), the other
at a higher level (HY). We describe the
evolution of this behavioral pattern along the
first year of life in both sublines and the
results of reciprocal crosses between them.
[...]
Discussion : Research in yawning
behavior has moved during the past decade from a
rather neglected position to become a field of
rapidly growing interest, particularly for
neuropharmacologists. With the aim of developing
better experimental subjects for the
physiological analysis of this behavior, we have
endeavoured to obtain inbred genetic sublines of
Sprague-Dawley rats with high and low
spontaneous yawning rates.
The increase in yawning activity in HY males
was observed from the very beginning of
inbreeding, the differences between homologous
generations of HY and LY rats being highly
significant from F3 onwards. Yawning activity in
HY females is slightly but significantly higher
than in LY females. In both sublines females
yawn much less than males, confirming the sexual
dimorphic character of this behavior.
We feel it must be stressed that the
quantitative data on yawning here reported have
been obtained under very strictly standardized
observational conditions (see Methods), which
have been maintained during almost 8 years.
Yawning frequency in HY animals is more
susceptible than in LY rats to changes in the
conditions under which the animals are observed:
it decreases during social interaction with
other littermates when animals are placed in
collective cages; it increases, due to
habituation to being placed singly in novel
environments, when observation sessions are
repeated at daily intervals; it also has an
important circadian variation.
Yawning activity increases with age. Young
and adult rats yawn at a higher rate than infant
animals. It is well known that at puberty there
is an important increase in testosterone levels
in male rats and it has been demonstrated that
the administration of this sex hormone promotes
an important increase in yawning frequency both
in female rats and castrated males. However, we
have not found any différence in the
serum levels of testosterone between HY and LY
rats, so we are inclined to discard androgenic
hormonal factors as contributors to the
difference in yawning rates observed between
these two sublines (Eguibar et al., unpublished
results).
Biometrical analysis of non-segregating
populations (Pl, P2 and FI) after reciprocal
genetical crosses between animals of the HY and
LY sublines, suggested that one pair of genes is
involved in the difference between these
sublines and that the LY (P 1) subline is
partially dominant over the HY (P2) one. Since
no differences were found between reciprocal FI
or F2 generations, maternal factors may be
excluded.
Yawning behavior is subject to important
dopaminergic (inhibitory) and cholinergic
(excitatory) influences 15,33. If tonic
doparninergic inhibitory control diminishes,
yawning frequency increases. The same happens
with an increase in cholinergic activity. Thus,
on a still rather loose conjectural basis, we
think that HY rats may have a higher tonic
cholinergic activity than LY animals. An
increase in cholinergic tone in HY rats could be
understood as a direct and general effect,
intrinsic to the cholinergic system as a whole,
or an indirect and more particular phenomenon,
resulting from a decrease in tonic DA inhibitory
activity, and therefore restricted only to
cholinergic pathways subject to dopaminergic
restraining control. We do not yet have a
definite choice between these alternative
hypothetical possibilities, which are under
current experimental scrutiny with
pharmacological tools.
