Department of Psychobiology,
Escola Paulista de Medicina, Sao Paulo,
Brazil
Paradoxical sleep deprivation (PSD) induces
changes in behaviors induced by dopaminergic and
cholinergic agonists, including increased
aggressive behavior and stereotypy, decreased
number of yawns, and shedding of bloody tears in
male rats. In female rats, however, very little
is known about the relationship between PSD and
the effect of these drugs. The present study
sought to examine this issue. As in males, PSD
in females resulted in increased
apomorphine-induced stereotypy, decreased
pilocarpine-induced chromodacryorrhea, and
hyperthermia. Unlike males, however, no
apomorphine-induced aggressiveness or
apomorphine- and pilocarpine-induced yawning
were observed in PSD females. These findings
suggest that female sexual hormones may affect
the expression of some behaviors and not the
neurotransmission as a whole, because
drug-induced behaviors in PSD females were
partly similar to those observed in PSD
males.
INTRODUCTION
The introduction of methods for selective
deprivation of paradoxical sleep in both humans
and experimental animals provided us with a new
approach to in vivo investigation of its
functions. It is well established that
paradoxical sleep deprivation (PSD) in
experimental animals results in behavioral
changes, such as increase in aggressive behavior
induced by dopaminergic agonists, in stereotypy
, in locomotion, and in colonic temperature, and
decrease in number of dopaminergic and
cholinergic agonist-induced yawning.
The behavioral changes in response to
dopaminergic drugs following PSD can be
explained by either a supersensitivity of
dopaminergic postsynaptic or a subsensitivity of
dopaminergic presynaptic receptors. Some
reports, however, state that PSD induces
specific changes in the dopaminergic system,
such as increased density of D1 type receptors
in the mesolimbic pathway, which is not observed
in the corpus striatum in rats, and decreased
function of postsynaptic receptors in the
mesolimbic pathway, but not in the nigrostriatal
pathway in mice.
Catecholaminergic systems and sexual
steroids have central effects that are of
significance for the regulation of physiological
processes, including ovulation and copulatory
behavior. The expression of behaviors mediated
by both mesolimbic and nigrostriatal
dopaminergic pathways seems to be related
directly to the effects of ovarian hormones on
the central nervous system. For example,
ovariectomized female rats exhibit a decrease in
rotational behavior induced by both electric
stimulation and amphetamine. Administration of
physiological doses of es-
trogen in ovanectomized female rats
potentiates the release of dopamine and
amphetamine-induced rotational behavior.
Moreover, chronic administration of estradiol
increases the density of D2 type receptors in
corpus striatum.
Because female sexual steroids regulate
behaviors that are mediated by the dopaminergic
system, we investigated whether or not PSD
induces behavioral changes in non-ovariectomized
female rats. Behavioral (aggressiveness,
stereotypy, and yawning) as well as
physiological (colonie temperature) measurements
were taken for this purpose.
DISCUSSION
The results of the present study showed that
administration of a dopaminergic agonist (i.e.,
apomorphine), did not induce aggressive behavior
in either control or PSD females. These findings
differ from those reported for males.
Administration of high doses of dopaminergic
agonists to controls or low doses to PSD animals
result in increased aggressiveness. Studies
involving removal and/or administration of
testicular hormones reveal the importance of
androgens on the expression of aggressiveness.
Female rats, on the other hand, are generally
less aggressive than males. Under specific
circumstances, how ever, females show increased
aggressiveness, specially during pregnancy,
lactation, cohabitation with a sterile male,
competitive experiences, or repeated exposure to
unusual situations.
Several studies show a differential effect
of apomorphine in males and females. Thus,
contrary to males, very high doses of the
dopaminergic agonist do not induce aggressive
behavior in females. In additon, apomorphine
does not alter verticalization of stereotyped
behavior and colonic temperature. These gender
differences in the expression of aggressiveness
may suggest an important modulatory effect of
sexual hormones on the neural systems involved
with this class of behavior.
Our results on stereotyped behavior were
similar to those found for males. PSD animals
presented higher scores of stereotypy than
controls. Contrary to the males, however, I mg!
kg of apomorphine did not intensify stereotypy
in PSD females.
It is important to note that in intact
females apomorphine induced stereotypy does not
seem to correlate with any hormonal change
during the estrous cycle. Data (unpublished)
from our lab and others show that PSD interferes
with regularity of the estrous cycle. However,
each of our females had its estrous cycle
registered before behavioral testing. There was
no correlation between phase of the cycle and
behavioral manifestation. In ovariectomized rats
treated with estrogen and progesterone, however,
apomorphine-induced stereotypy is diminished
compared to that of untreated ovariectomized
females, suggesting a possible action of these
hormones upon dopaminergic transmission.
It is believed that stereotypy is a
consequence of dopaminergic stimulation of the
caudate nucleus. The lack of gender differences
on this kind of behavior (our findings compared
to those in males) suggests that sexual steroids
modulate this dopaminergic pathway in a similar
way. These findings confirm the results of
Jackson et al. and Kelly et al. who reported
that the expression of aggressiveness and
stereotypy may involve different dopaminergic
pathways.
Gender differences in apomorphine-induced
yawning was reported by Nickolson and Berendsen.
This study showed that males present a more
robust response to low doses of apomorphine than
females. Thus, the authors suggest that
apomorphine induced yawning is under the
influence of androgens and that estrogens play a
minor role on the mediation of this behavior. In
the present study, both control and PSD females
presented a very low number of apomorphine,? and
pilocarpine-induced yawning. This is in
discrepancy with the data for males, indicating
a reduction of yawning in 96-h PSD compared to
control animals (36). These results in females
may be due to the very low frequency of yawning
already seen in control rats. It is possible,
however, that female sexual hormones play a role
in the dynamics of the systems involved with
yawning behavior, masking the receptor
sensitization induced by PSD.
Chromodacryorrhea results from the
activation of muscarinic peripheral mechanisms.
Studies investigating the relationship between
the effects of PSD and cholinergic drugs in
males show that PSD inhibits the shedding of
bloody tears. Our study showed the same results
in females, suggesting that peripheral
mechanisms involved in this phenomenon are
similar for both genders. Finally, our results
of colonic temperature in females are in
agreement with studies investigating the
relationship between sleep and thermoregulation
in male rats, which report hyperthennia induced
by PSD .
Taken together, the results of the present
study indicate that female sexual hormones may
have a modulatory role on the dopaminergic and
cholinergic systems. Because the results in
females partly replicate those in males, we
propose that this class of hormones does not
alter the neurotransmission per se, but the
expression of behaviors mediated by these
systems.
-Hipolide DC;
Lobo LL; De Medeiros R; Neumann B; Tufik S
Treatment with dexamethasone alters yawning
behavior induced by cholinergic but not
dopaminergic agonist. Physiol Behav 1999; 65;
4-5; 829-32
-Hipolide
DC, Tufik S Paradoxical sleep deprivation in
female rats alters drug-induced behaviors
Physiol Behav. 1995; 57; 6; 1139-1143
-Mogilnicka E,
Klimek V Drugs affecting dopamine neurons
and yawning behavior. Pharmacol Biochem Behav
1977; 7; 303-305
-Molgilnicka
E REM sleep deprivation changes behavioral
response to catecholaminergic and serotoninergic
receptor activation in rats Pharmacol Biochem
Behav 1981; 15; 1; 149-151
-Neumann BG,
Troncone LR, Braz S, Tufik S Modifications
on dopaminergic and cholinergic systems induced
by the water tank technique: analysis through
yawning behavior Arch Int Pharmacodyn Ther 1990;
308; 32-8
-Stoessl
AJ Effects of ageing on the behavioural
responses to dopamine agonists: decreased
yawning and locomotion, but increased stereotypy
Brain Research 1989; 495; 20-30
-Tufik S et
al Effects of stress on drug induced yawning
Physiology & behavior 1995; 58; 1;
1881-184
-Tufik
S Does REM sleep deprivation induce
subsensitivity of presynaptic dopamine or
postsynaptic acetylcholine receptors in the rat
brain? European Journal of Pharrnacology 1987;
140; 215-219
