- Young male albino rats yawn significantly
more than females or castrated males when
injected with physostigmine (0.10 mg/kg).
Treatment with testosterone (100 µg daily)
during seven days restores cholinomimetically
induced yawning in castrated males, and
increases yawning in normal and androgenized
females. Treatment with estradiol (200 µg
daily) during one week does not modify
physostigmine induced yawning behavior in
castrated males nor in androgenized fernales.
Although yawning is a simple behavioral item
not obviously related to the sexual sphere,
several reports have appeared pointing towards a
curious association between yawning and some
elements of sexual behavior. Injections of ACTH,
MSH, or peptides possessing similar hormonal
activity, into the cerebrospinal fluid or the
brain, induce a peculiar stretching and yawning
syndrome (SYS) in several animal species (6, 7).
The same treatment also produces a display of
sexual excitement, both in male (2, 3) and
female rabbits (1). Associated yawning and
penile erections have been observed during and
between waves of cortical spreading depression
in male rats (4). Jakobartl and Huston (16) have
recently suggested that both the SYS and the
penile erections observed after intracranial
injections of ACTH (and other peptides) could be
after-effects of spreading depression produced
by these substances. With low doses of
apomorphine and other dopaminergic agonists
injected systemically, Mogilnicka and Klimek
(18) have also observed associated yawning with
penile erections in adult rats, observation
which we have confirmed (unpublished
Even if little or no sex differences exist in
the SYS induced by ACTH (1), the release of
yawning behavior in monkeys in response to their
mirror images seems to be sex-bound: Hall (10)
mentioned that females in this experimental
situation rarely "yawned".
Cholinomimetically-induced yawning in adult rats
also seems to be sex dependent: males injected
with physostigmine yawn significantly more than
females (21). In the present report we describe
some experiments which suggest that cholinergic
yawning is subject to distinct sex hormone
Young male albino rats, 30-day-old, injected
intraperitoneally with physostigmine salicylate
(0.10 mg/kg, as base), and observed during one
hour as formerly described (13, 22), yawn
significantly more than female littermates, or
males castrated when 11 day old. This age for
testes ablation was selected so as not to
interfere wiih the perinatal critical period of
hormonal masculinizing effects on the CNS, and
distant enough from the first test with
physostigmine for the effects of castration to
become evident. Castrated males treated with
daily injections of testosterone (100 µg)
from the 30th to the 37th day, are
undistinguishable from intact males in their
yawning response to the anticholinesterastic
drug. Such restoration of yawning is not
obtainable by treatment with estradiol benzoate
(200 µg daily).
A single androgenizing (19) injection of
testosterone (250 µg) to one-day-old female
rats (n = 16) does not modify the
physostigmineinduced yawning response tested on
the 30th postnatal day, when compared to that of
normal females (n = 16) (Fig. 2). A second test,
performed on the 37th day, after one week
treatment with testosterone (100 µg daily),
demonstrated highly significantly increased
yawning responses in both groups, in comparison
to their responses in the first test (P <
0.001, Mann-Whitney U Test) (20). The difference
in yawning frequency between normal and
androgenized females after this treatment is
also statistically significant (P < 0.01),
the average number of yawns of the latter group
being more than 1000/o higher than in the
former, during one hour after physostigmine
It is unlikely that so important quantitative
differences in cholinomimetically induced
yawning between male and female rats are due to
simple pharmacokinetic effects, as have been
described for other drugs. These are generally
interpreted as the result of sex hormone
influences upon microsomal enzymes participating
in drug metabolism, androgens stimulating, while
estrogens and progesterone inhibit microsomal
enzymes activity (5). Therefore, the greater
yawn promoting effect of physostigmine in male
rats, compared to females, in testosterone
treated castrated males compared to the
untreated castrates, and in testosterone treated
females compared to normal females, could hardly
be understood as due to pharmacokinetic
effects of testosterone on the metabolism of
physostigmine. These would rather tend to
reduce than to increase the anticholinesterasic
action of physostigmine.
The greater yawning-inducing effect in
testosterone treated neonatally androgenized
females is also consistent with the idea that
the differences observed are the result of true
androgenic hormonal effects exerted upon the
central nervous system, both at an early
(perinatal) period of development, and later on
in life. In the particular effect analyzed by
us, testosterone treatment of one-day-old
females seems to have increased their
sensitivity to testosterone administrated one
month later. The level of the central nervous
system at which testosterone might interact with
the neural structures responsible for
cholinomimetically induced yawning is unknown,
and only broad hypothetical suggestions may be
advanced. Because of the early ontogenetic
maturation of cholinergic yawning (13, 21), it
has been suggested that the neural circuitry
responsible for yawning behavior seems to be
localized at the lower brainstem region. The
observation of yawning in Gamper's mesencephalic
human being (17) also points in that direction.
This does not necessarily mean that the
influence of testosterone is exerted at such a
caudal level, because it might also be mediated
by descending pathways from higher placed
nervous sites, i.e. in the limbic system, well
known as steroid hormone targets.
Although the described effect of testosterone
is upon a behavioral pattern including important
cholinergic links, the hormonal action might as
well take place in cholinergic or
cholinosensitive neurons, or in neurons of some
of the specific monoamine pathways, which could
exert some modulating influences on yawning.
Such alternatives should be considered when
reports have appeared describing yawning in
adult rats evoked by dopaminergic agonists (18),
and a strong facilitation of
physostigmine-induced yawning by Lu 10-171 (22),
a potent and selective serotonin uptake
inhibitor (15). Sex differences and the effect
of gonadal steroids on brain serotonin levels,
5-HT synthesis or turnover have been the subject
of research by several groups in recent years
(4, 8, 9, 11, 12) but the results remain
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above described hormonal effects on yawning are
obscure, they do confirm the possibility
envisaged by Young et al (23) that "gonadal
substances may affect behavior beyond that which
is primarily sexual in the sense of being
directed solely towards the attainment of sexual
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« It is
ironic that testosterone "the male sex hormone,"
is more closely associated with the yawning rate
than with the mounting or intromitting rates
» Charles Phoenix
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- credit photo : "Asif A. Ghazanfar
and Aristides Arrenberg"
- Max Planck Institute for
- merci à eux