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Research report
Abstract
b-Endorphin is an endogenous opioid peptide that is released during stress and has been associated with many physiological functions.
In this experiment b-endorphin deficient mice were used to study the role of endorphins in the acute physiological and behavioral
responses to a social conflict, as well as their role in social stress-induced changes in sleep. Adult male b-endorphin deficient and wild
type mice were subjected to the stress of a 1 h social conflict with an aggressive dominant conspecific. After the conflict, the b-endorphin
deficient mice had higher corticosterone levels but the peak increase in body temperature was not different from that in wild type animals.
In fact, body temperature returned to baseline levels faster in the b-endorphin deficient mice. During their interaction with the aggressive
conspecific several of the b-endorphin deficient mice showed clear signs of counter aggression whereas this was not seen in any of the
wild type mice. Overall, the b-endorphin deficient mice and wild type mice had fairly similar sleep patterns under baseline conditions and
also showed similar amounts of NREM sleep, REM sleep and EEG slow-wave energy after the social conflict. In addition, no differences
were found in the sleep patterns of mice that showed counter aggression and mice that did not. In conclusion, the results suggest that
b-endorphin modulates the acute endocrine, thermoregulatory and behavioral response to a social conflict but the data do not support a
major role for b-endorphin in the regulation of sleep or social stress-induced alterations in sleep.
2003 Elsevier Science B.V. All rights reserved.
Theme: Neural basis of behavior
Topic: Stress
Keywords: Social conflict; Aggression; Opioid; Glucocorticocoid; Body temperature; REM sleep
1. Introduction
b-Endorphin is an endogenous opioid that acts as a
neuropeptide within the central nervous system and functions as a hormone in the periphery upon release in the
blood stream [1,6]. In the brain, b-endorphin producing
cells are found in the hypothalamic arcuate nucleus and the
caudal nucleus tractus solitarius, which together have
extensive projections throughout the brain [15]. The neurons of the arcuate nucleus innervate other hypothalamic
regions, structures of the limbic system, and various areas
in the brain stem. Also the nucleus tractus solitarius
*Corresponding author. Department of Molecular Neurobiology, University of Groningen, P.O. Box 14, 9750 AA Haren, The Netherlands.
Tel.: 131-50-363-2334; fax: 131-50-363-2331.
E-mail address: p.meerlo@biol.rug.nl (P. Meerlo).
0006-8993 / 03 / $ see front matter 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016 / S0006-8993(03)02805-1
170
brain area and the receptor types that are activated, but a
number of studies report increased signs of NREM sleep
[9,27]. In cats, similar to opioid effects in humans, bendorphin may cause a strong reduction in REM sleep
[16].
Interestingly, some of the reported effects of exogenous
b-endorphin administration mimic the effects of social
defeat stress on sleep in rodents. In particular, mice rapidly
overcome the arousal that is induced by a social conflict
and show an increase in NREM sleep afterwards, while
REM sleep, on the other hand, is strongly suppressed [20].
It is known that a social conflict in rodents activates central
and peripheral opioid systems and causes an increase in
b-endorphin levels [8,13,22,30,31], particularly in defeated
animals as compared to dominants [8,13]. In the present
study, experiments were performed with b-endorphin
deficient mice to determine the role of endorphins in the
physiological and behavioral response to a social conflict
and, in particular, the role of b-endorphins in sleep and
social stress-induced changes in sleep. If b-endorphins
would facilitate NREM sleep and inhibit REM sleep after
social defeat stress, one would expect a prolonged period
of wakefulness but a less pronounced decrease in REM
sleep after a conflict in b-endorphin deficient mice.
171
3. Results
2.4. Statistics
For statistical analysis of body weight and corticosterone
levels, two-sample t-tests were applied. Also the average
24- and 12-h light / dark values of body temperature during
baseline were analyzed with two-sample t-tests. In addition, for 1- and 6-h values of body temperature and sleep
data, repeated measures ANOVA was performed with a
factor genotype (wildtype vs. b-endorphin deficient) and a
factor time (1-h blocks and 6-h blocks). For body temperature and sleep after the conflict, the deviations from the
corresponding baseline values were calculated. When
ANOVA revealed an overall effect of genotype or a
genotype3time interaction, separate blocks were tested
with two-sample t-test. Within each genotype, data collected on the experimental day were compared with
corresponding baseline values using a paired t-test.
172
Fig. 2. Average hourly values of body temperature measured in wild type mice (left) and b-endorphin deficient mice (right) under baseline conditions (s)
and on the experimental day (d) when the animals were subjected to the stress of a 1-h social conflict during the 6th hour of the light phase. Dark bars
above the graph indicate the dark phase. Significant differences: B, relative to baseline (paired t-test, P,0.05); *, relative to wild type (two-sample t-test
for deviations from baseline, see text).
173
Fig. 3. Cumulative NREM sleep SWE, NREM sleep and REM sleep per 6-h interval in wild type mice (left) and b-endorphin deficient mice (right) under
baseline conditions (s) and on the experimental day (d) when the animals were subjected to a 1-h social conflict during the 6th hour of the light phase.
Data are expressed as averages (6S.E.M.). Significant differences: B, relative to baseline (paired t-test, P,0.05); *, relative to wild type (two-sample
t-test).
174
4. Discussion
After a social conflict, b-endorphin deficient mice had
higher corticosterone levels than wild type animals while
the peak temperature increase was not different between
the genotypes. In fact, body temperature returned to
baseline levels faster in the b-endorphin deficient mice.
During the interaction with an aggressive dominant conspecific, several of the b-endorphin deficient mice showed
clear signs of counter aggression whereas this was not seen
in any of the wild type mice. Overall, the b-endorphin
deficient mice and wild type mice had fairly similar sleep
patterns under baseline conditions and they showed similar
changes in the amount of NREM sleep, REM sleep and
accumulated SWE in response to a social conflict. In
addition, no differences were found in the sleep patterns of
mice that showed counter aggression and mice that did not.
Thus, these data do not support our hypothesis that bendorphin facilitates NREM sleep and suppresses REM
sleep after a social conflict. Although the complete lack of
endorphins from early development onwards might result
in mechanisms that compensate for this deficiency [10,29],
the present study demonstrates that the typical sleep
pattern after social defeat stress can still occur in the
absence of b-endorphin.
Our finding of an increased body weight in b-endorphin
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
Acknowledgements
[19]
[20]
[21]
[22]
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