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Sleep and Biological Rhythms
https://doi.org/10.1007/s41105-018-0166-6
ORIGINAL ARTICLE
Evaluation of behavior and endocrinological changes after REM sleep
deprivation-induced mania-like behavior in mice
Saiful Alom Siddique
1
· Thangavel Tamilselvan
1
· Manikkannan Vishnupriya
1
· Elumalai Balamurugan
1
Received: 23 January 2018 / Accepted: 17 May 2018
© Japanese Society of Sleep Research 2018
Abstract
The pressure to stay up longer in our modern society due to constant exposure to artificial light and interactive activities;
furthermore, social and economic pressures impact human physiology and behavior. Rapid eye movement sleep deprivation
(REMSD) alters most of the hormones, which may have adverse behavioral changes and other health consequences like
mania and other psychiatric disorders. The exact role of REMSD-altered hormonal levels and the manner in which emerging
consequences lead to mania-like behavior is poorly understood. Thus, we sought to verify the behavior and endocrinological
changes after 48, 72, and 96 h of REMSD-induced mania-like behavior in mice. We performed modified multiple platform
method of depriving the REM sleep for 48, 72 and 96 h, respectively, and one group maintained as a control. Motor assess-
ment and aggressive behavior were determined by IR-Actimeter and Resident Intruder Test. Quantitative determination of
serum thyroid hormones (TSH, T4, and T3), testosterone, corticosterone (CORT), prolactin (PRL), adrenocorticotropic
hormone (ACTH), oxytocin (OT) and melatonin (MT) concentrations were determined by ELISA method. After respective
hours of REMSD, the higher locomotion noticed among all REMSD mice and also showed higher aggressive behavior com-
pared with control. Concentration of serum TSH and T4 was declined and elevated the T3, PRL, CORT, testosterone, ACTH,
OT and MT levels in REMSD mice. These experiments showed that concentrations for the majority of the studied hormone
and behavior were disrupted during REMSD. Our study indicated that REMSD results in mania-like behavior in mice and
associated disruption to hormonal levels, although the exact mechanisms by which these take place remain to be determined.
Keywords REMSD · Mania · Bipolar disorder · Hormones · Aggressive behavior · Locomotor activity
Introduction
Rapid eye movement sleep (REMS) is a unique stage of
sleep that is expressed in all higher order vertebrates, includ-
ing mammals [1]. Chronic sleep loss would be a common
feature in modern society, and one of the consequences of
sleep loss is the impairment of cognitive function. Millions
of people worldwide experience REM sleep deprivation
(SD) on a daily basis [2]. The pressure to stay up longer in
our modern 24/7 society impacts a growing percentage of
the population [3]. A population-based study indicated that
over the past 50 years, sleep duration in adult and adolescent
Americans has declined by 1.5–2 h per night, with 30%
reporting sleep of 6 h per night or less [4].
In particular, REM sleep has a strong effect on the levels
of some hormones rather than NREM sleep. REMSD alters
some numerous hormones, which may have adverse behav-
ioral changes and other health consequences. In addition,
reduced need for sleep is a symptom of manic and hypo-
manic episodes [5].
Bipolar disorder (BD) is a mood disorder, characterized
by long-term episodic, cyclical patterns involving extreme
fluctuations of mood that cause significant disruptions in
one’s interpersonal, occupational and social life [6]. Mania
or manic episodes are most often associated with BD. The
World Health Organization (WHO) has identified BD as the
6th most disabling conditions globally, in its ‘The Global
burden of disease’ report [7]. Suicide is a frequent cause of
death in BD patients [8].
Disturbances of affect and mood, such as major depres-
sion and bipolar affective disorder, are associated with
* Elumalai Balamurugan
balamurugan_au@yahoo.co.in
1
Department of Biochemistry and Biotechnology, Faculty
of Science, Annamalai University, Annamalainagar,
Tamilnadu 608 002, India
@Phil_Robichaud
@deepthiw
@JoseServera