Abstract
Repeated exposure to an anxiogenic stressor (AS) is a known environmental factor for the development of depression, yet the progression of sleep-wake (S-W) changes associated with the onset of AS-induced depression (ASID) is not completely understood. Thus, the aim of this study was to identify these progressive S-W changes by developing ASID in rats, via repeated exposure to an AS, and compare this ASID-associated sleep phenotype with the sleep phenotype of human depression. To achieve this aim, rats were first recorded for a 6 h period of baseline S-W activity without AS. Then, rats were subjected to 5 days of AS [Day 1: inescapable foot-shock; 5 trials of 3 s foot-shocks (1.0 mA) at 3 min intervals; Days 3–5: 15 trials of 5 s foot-shocks at 45 s intervals]. S-W activity was recorded for 6 h immediately after each AS treatment session. Two days later rats were again recorded for 6 h of S-W activity, but with no exposure to the AS (NASD). Compared to the baseline day: Day 1 of AS (ASD-1) increased wakefulness, slow-wave sleep (SWS) latency, and rapid-eye movement (REM) sleep latency, but decreased the total amount of REM sleep; ASD-2 animals remained awake throughout the 6 h S-W recording period; ASD-3, ASD-4, and ASD-5 (ASDs-3–5) decreased wakefulness, SWS latency, and REM sleep latency, but increased the total amount of REM sleep. Interestingly, these results reveal that initial exposure to the AS versus later, repeated exposure to the AS produced opposing S-W changes. On NASD, animals exhibited baseline-like S-W activity, except slightly less REM sleep. These results suggest that repeated AS produces a sleep phenotype that resembles the sleep phenotype of depression in humans, but consistent re-exposure to the AS is required. These results are promising because the methodological simplicity and reversibility of the ASID-associated S-W phenotype could be more advantageous than other animal models for studying the pathophysiological mechanisms that underlie the expression of ASID.
Highlights
Endogenous depression is a debilitating mental health disorder that currently affects about 121 million people worldwide, contributing to the loss of approximately 850,000 lives each year
The effect of shock treatment on the percentages of time spent in W, slow-wave sleep (SWS), transitional sleep between SWS and REM sleep (tS-R), and rapid-eye movement (REM) sleep were statistically analyzed using a two-way ANOVA followed by Bonferroni post tests, with time as a repeated-measure variable and treatment as a between-subjects variable
EFFECTS ON SLEEP-WAKE ARCHITECTURE Figure 1 shows the representative S-W architectures of a single rat for the 6 h recordings (10:00 a.m. to 4:00 p.m.) that immediately followed baseline, shock, and no shock session. These S-W architectures show that ASD-1 produced a massive increase in REM sleep latency and fewer REM sleep episodes compared to the baseline
Summary
Endogenous depression is a debilitating mental health disorder that currently affects about 121 million people worldwide, contributing to the loss of approximately 850,000 lives each year (http://www.who.int/mental_health/management/ depression/definition/en/). It is characterized by a multitude of symptoms that have emotional, behavioral, and physical aspects (Fawcett and Kravitz, 1983). The most common cognitive symptoms in depressed patients are difficulty thinking, concentrating, and decision-making (Ciraulo and Shader, 2011). Since depression impacts all body systems, it is not surprising that investigators have attempted to determine the effects of depression on many biological markers, including sleep architecture, hormones, neurotransmission, brain imaging, and immune function in order to identify the underlying neuropathology of depression (Coble et al, 1976; Kupfer, 1976, 1978; Gillin et al, 1979; Reynolds and Kupfer, 1987; Kroenke and Price, 1993; Sharpley and Cowen, 1995; Posse and Hällström, 1998; Ciraulo and Shader, 2011; Goldstein et al, 2012)
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