Several recent reports indicate that
estrogens are capable of modulating dopamine
(DA) receptor sensitivity in experimental
animals.
The data concerning the capacity of
estrogens to influence postsynaptic DA receptors
are controversial. Supersensitivity of DA
receptors induced by various estrogen treatments
is suggested by the fact that these treatments
enhance apomorphine- and amphetamine-induced
stereotypy, increase circling behavior in
6-OH-DA-lesioned animals and increase [3
Hspiroperidol binding sites in the striatum
(Hruska and Silbergeld, 1980). Other authors
have however, reported that estrogens reduced
apomorphine-induced stereotypy, the circling
behavior elicited by apomorphine in rats with a
unilateral lesion of the entopeduncular nucleus
and the increase in striatal acetylcholine
levels observed after dopamine agonists. These
discrepancies may be partially explained by the
different schedules used, such as different
estrogen dosage, length of hormone treatment,
intervals between treatment and challenge with
DA agonists and dosage of agonists.
Contrary to what was observed for
postsynaptic DA receptors, all reports
concerning the influence of estrogens on DA
autoreceptor sensitivity suggest that these
receptors become subsensitive after estrogen
treatment. Indeed, Chiodo and Caggiula (1980)
reported that estrogens significantly decreased
apomorphine inhibition of the firing of DA
neurons in the rat substantia nigra. Piccardi et
al. (1983) reported that estrogens antagonized
both the hypomotility and the decrease in
stnatal DA turnover induced by low doses of
apomorphine and other DA agonists in rats.
Moreover, these authors found that apomorphine
was less effective in decreasing motility and
striatal DA turnover in female than in male rats
(Piccardi et al., 1983), suggesting that
endogenous estrogens reduce DA autoreceptor
sensitivity.
Small doses of apomorphine also elicited
repeated episodes of yawning in rats (Molginicka
and Klimek, 1977; Serra et al., 1983),
suggesting that the DA receptors mediating
yawning may have pharmacological properties
similar to those of DA autoreceptors. Thus, in
order to clarify whether estrogens modify the
sensitivity of the DA receptors mediating
yawning, we studied the estrogen effect on
apomorphine-induced yawning in rats.
The results indicate tha short-term
treatment with the 17B-estradiol benzoate
antogonized apomorphine induced yawning in male
rats. Morover, apomorphine appeared to be less
effective in inducing yawning in female than in
male rats.
Discussion
The present results indicate that
exogenously administrered estrogens antagonize
apomorphine-induced yawning in male rats.
Moreover, in agreement with a previous report
(Berendsen and Olson, 1981), they show that
apomorphine is less effective in inducing
yawning in female than male rats.
Although estrogens are known to alter the
metabolism of various drugs, it can be excluded
that the effect of these hormones on the
response to apomorphine depends on alterations
in the metabolism of the drug, since the
half-life of 3H apomorphine in the plasma of
rats treated with estrogens is not significantly
changed (Gordon et al., 1980).
Since apomorphine-induced yawning is
considered to be due to stimulation of DA
receptors in CNS (Mogilnicka and Klimek, 1977;
Serra et al 1983), subsensitivity of these
receptors may explain the reduction of this
behavioral response served in males following
estrogen treatment or in normal female
animals.
Until now, these receptors have been
identified with DA autoreceptors (Mogiinicka and
Klimek, 1977; Serra et al., 1983), which mediate
apomorphine-induced hypomotility, decrease DA
synthesis and release and inhibition of
dopaminergic firing. This hypothesis is
essentially supported by the observation that
the doses of apomorphine needed to produce
yawning are in same range as those needed to
stimulate DA autoreceptors. Therefore, according
to this hypothesis, yawning may be a behavioral
correlate of the inhibition of DA transmission
in the CNS.
However, our recent results suggest that
dopaominomimetic drugs induce yawning by
stimulating postsynaptic DA receptors in the
CNS. Indeed, the selective stimulant of DA
autoreceptors, (- )- 3PPP (Hjorth et al., 1983),
fails to induce yawning in rats while (+)-3PPP,
which stimulates DA autoreceptors as well as
postsynaptic DA receptors (Hjorth et al., 1983),
induces repeated episodes of yawning (Serra et
al., 1984). Thus, it may be suggested that
stimulation of apomporphineinduce yawning by
stimulating a special kind of postsynaptic DA
receptor with an affinity for DA agonists
similar to that of DA autoreceptors. According
to this hypothesis, yawning could be considered
the step in the arousal responses induced by the
stimulation of DA transmission in the CNS, which
culminate in the appearance stereotypy when
higher doses of dopaminomimetic drugs are
administered.
Irrespective of the nature and anatomical
location of DA receptors mediating yawning, the
finding that they become subsensitive in male
animals treated with estrogens and that they
appear to be subsensitive in female rats may
contribute to explain the physiological
significance of yawning. Some observations have
suggested that yawning is a behavior more
typical of the male animal. Indeed, yawning is
usually related to the display of social
dominance by male monkeys and is often
associated with mounting behavior when male
monkeys are paired with female partners (Goy and
Resko, 1971). Moreover, in his description of
the behavior of monkeys towards mirror images,
Hall (1962) observed that among the arousal
responses in the adult male animal yawning was
very frequent and at times accompanied by penile
erection, while the adult female "...rarely, if
ever, yawned."
