A number of the emotional, mental, and physical symptoms of depression can be associated with S-W disturbances (Harrison and Horne, 2000
; Wagner et al., 2001
;Smith and Haythornthwaite, 2004
; Walker and van der Helm, 2009
). Common S-W disturbances in depression include a decrease in REM sleep latency, greater frequency of REM sleep earlier in the night, sporadic bouts of wakefulness (W), early morning awakenings, reduced duration of stage 3 and stage 4 SWS, and increased duration of stage 1 SWS (Coble et al., 1976
; Kupfer, 1976
; Gillin et al., 1979
; Reynolds and Kupfer, 1987
; Sharpley and Cowen, 1995
). The principal findings of this study are: (1) ASD-1 increased the total percentage of time spent in W, SWS latency, and REM sleep latency; and decreased total percentages of time spent in SWS, tS-R, and REM sleep, and the number of REM sleep episodes. (2) ASD-2 eliminated sleep altogether (100% W). (3) ASDs-3–5 decreased the total percentage of time spent in W, SWS latency, and REM sleep latency; and increased total percentages of time spent in tS-R and REM sleep, and the number of REM sleep episodes. (4) On NASD, the total percentage of time spent in SWS, SWS latency, REM sleep latency, and the number of REM sleep episodes all reverted back to BLD levels; the total percentages of time spent in W and tS-R remained at decreased levels similar to ASDs-3–5; and the total percentages of time spent in REM sleep decreased to levels between those of ASD-1 and the BLD. Collectively, these results partly validate the ASID paradigm used in the present study as a suitable animal model for studying the sleep phenotype of depression, in so far as this model’s validity depends on continued stressor exposure. However, a caveat of this interpretation is that, in the present study, we did not directly measure the behavioral signs of depression. Thus, a future study is needed to verify that the ASID model induces depression similar to other animal models of depression.
The results of the present study show that after ASD-1, rats exhibited increases in the amount of time spent in W, which were consistent throughout the entire 6
h S-W period. This increase in W was accompanied by increases in the latencies of SWS and REM sleep and decreases in the amount of time spent in SWS, tS-R, and REM sleep. On ASD-2, the loss of sleep was even more pronounced. The loss of sleep and increase in W demonstrated on these 2
days are typical characteristics of anxiety in both humans and animals (Monti and Monti, 2000
; Lavie, 2001
; Ohayon and Roth, 2003
; Maclean and Datta, 2007
; Pawlyk et al., 2008
; Sanford and Yang, 2010
; Macone et al., 2011
; Yang et al., 2011
). Contrary to the results of the present study, the previous studies that examined S-W changes associated with the LH model showed that SWS increases after the first day of LH training (Adrien et al., 1991
; Fogel et al., 2011
). This discrepancy could be explained by the fact that, as explained in the Introduction, these two prior studies incorporated learning components, and learning and memory has been shown to increase sleep (Karni et al., 1994
; Smith, 1995
; Stickgold et al., 2000
; Walker et al., 2002
; Huber et al., 2004
). However, a future study is necessary to confirm this interpretation.
Contrary to ASD-1, ASDs-3–5 produced reductions in W, as well as corresponding decreases in SWS latency and REM sleep latency. There were also significant increases in both the amount of time spent in REM sleep, during the first 2
h, and number of REM sleep episodes. Interestingly, these S-W changes are typical of those observed in human depression (Coble et al., 1976
; Garcia-Rill et al., 2008
). These very similar S-W profiles on ASDs-3–5 indicate a stabilized and sustained level of S-W activity resembling that of human depression. However, to our surprise, 2
days after the last AS session when animals were not re-exposed to the AS, the ensuing S-W activity reflected a very different sleep profile. Specifically, the amount of time spent in SWS, SWS latency, REM sleep latency, and the number of REM sleep episodes all returned to BLD levels. Interestingly, REM sleep during the first 2
h of recording also returned to within range of BLD levels, yet it was significantly decreased during the latter portion of the 6
h S-W period. Therefore, lack of re-exposure to the AS yielded S-W parameters that did not resemble normal baseline sleep or the S-W phenotype typical of ASID. This indicates that AS effectively produced a depression-like sleep phenotype and that anxiety is a necessary precursor of depression in rats.
In evaluating the significant outcome of this study, we acknowledge that certain aspects of the present study could be viewed as major limitations. The first of which is the fact that the present study did not employ a triadic design. However, the need for this specific design was mitigated, as the objective of this study was to examine changes in S-W activity within the same animal. Thus, baseline S-W activity for a specific animal served as the control S-W data for that individual animal and was then used to compare with that same animal’s S-W activity after exposure to an AS. Also, a potential limitation inherent in sleep studies that employ only a single experimental group is the fact that S-W patterns over time are subject to sequential dependencies. However, this variable was negated in the present study during the habituation recording sessions during which rats’ S-W activity stabilized (Datta, 2000
). This ensured little-to-no day-to-day variability in S-W patterns, allowing us to isolate the AS treatment-associated S-W changes. Finally, one additional caveat of this study, as explained earlier, is the fact that, other than S-W activity, no behavioral signs of depression were measured to confirm depression in ASID rats.
In summary, the ASID paradigm produces a sleep phenotype similar to that observed in humans with depression. Ultimately, this model could be used to study the sleep phenotype and pathophysiological mechanisms of stress-induced depression in the rat model. However, one important factor of this model is that maintaining a depression-like sleep phenotype in rats requires continual exposure to the stressor, and that sudden cessation of AS exposure appears to alleviate the depression-like S-W changes. This in turn suggests that the identification and elimination of anxiety could be a critical step for the development of behavioral and/or pharmacological therapies for treating depression.