Roles of Hypothalamic Subgroup Histamine and Orexin Neurons on Behavioral Responses to Sleep Deprivation Induced by the Treadmill Method in Adolescent Rats

Abstract

Abstract. Sleep deprivation induces several negative effects on behavior, emotion, attention, and learning ability. Sleep appears to be particularly important during adolescent brain development. In the present study, we examined the effects of sleep deprivation on behavior and hypothalamic neurotransmission including histamine and orexin neurons in adolescent rats using the treadmill method. Adolescent male rats were divided into three groups: treadmill sleep-deprived, treadmill control, and cage control groups. Energy expenditure, anxiety-like behavior, and locomotor activity were examined among the three groups. Histamine concentration in the cortex and diencephalon and the number of c-Fos-positive neurons in the hypothalamus were also examined. In addition, histamine and orexin neurons in the hypothalamus were simultaneously identified using rat histidine decarboxylase and orexin-A immunohistochemistry, respectively. Both energy expenditure and anxiety-related behavior significantly increased by the experimental 3-day sleep deprivation, while exploratory locomotor activity significantly decreased. Histamine contents did not change in the cortex, but significantly decreased in the diencephalon of sleep-deprived rats. Increased expression of c-Fos-positive neurons, including subgroup histamine and orexin neurons, was observed in the hypothalamus. These findings indicate that sleep deprivation increases energy expenditure and anxiety in adolescent rats and provide evidence for the pivotal role of hypothalamus subgroup histamine and orexin neurons in the behavioral response to sleep deprivation.

Sleep and obesity: A focus on animal models

“…The relationship between sleep, body weight, physical inactivity and metabolism has been further supported by sleep deprivation studies, which have been reviewed (Everson and Toth, 2000; Novati et al, 2008; Ramanathan et al, 2002; Ramanathan et al, 2010; Rechtschaffen et al, 2002; Reynolds and Banks, 2010; Xu et al, 2010). A series of early animal studies showed that sleep deprivation by the disc-over-water (DOW) method resulted in weight loss (Rechtschaffen and Bergmann, 1995), unlike weight outcomes in human sleep deprivation studies.…”

Sleep Deprivation and Gene Expression

“…Another common procedure to keep animals awake is the use of motorized treadmills or wheels (Guzman-Marin et al 2005, 2006Roman et al 2005;Xu et al 2010). This approach is thought to be less stressful than the flowerpot method, but the continuous forced activity, even though it is generally at a rather slow pace, may have effects unrelated to sleep loss per se.…”

Neurobiological Consequences of Sleep Deprivation

“…One study reports that, 72 h of REM SD in mice results in anxiogenic behaviors in the elevated plus maze and standard open field tests of anxiety [134]. Furthermore, 72 h treadmill induced SD is reported to increase anxiety-like behavior in open-field and elevated-plus maze tests [127]. SD for 72 h induced by grid suspended over water method caused anxiety-like behavior when tested in mirror chamber, elevated plus maze and zero maze tests [126] in addition to weight loss and impaired locomotor activity [124].…”