Sleep in the Wistar-Kyoto rat, a putative genetic animal model for depression

Abstract

The Wistar-Kyoto (WKY) rat exhibits several behavioral and hormonal abnormalities often associated with depression. One of the hallmarks of depression consists of alterations in the sleep-wake cycle, particularly in rapid eye movement (REM) sleep. If the WKY rat is indeed an animal model for depression, we hypothesized that it should also show sleep abnormalities relative to the control strain, the Wistar (WIS) rat Under baseline conditions, WKY rats showed a 50% increase in total REM sleep time during the 12 h light phase and an increase in sleep fragmentation during both the light and dark phase. The WKY rats also exhibited lower EEG power densities over the entire frequency range (0.2-25.0 Hz) during REM sleep. After a 6 h sleep deprivation, the REM sleep rebound was more pronounced during the dark but not the light phase in the WKY rats. Since the WKY rat represents a genetic model for depression with altered EEG sleep patterns, this strain may be particularly useful for investigating the relationship between depression and sleep abnormalities.

Homeostatic Regulation of Sleep in a Genetic Model of Depression in the Mouse: Effects of Muscarinic and 5-HT1A Receptor Activation

“…Globally, H mice had fragmented sleep, with notably a shorter duration of SWS bouts and a greater number of wake episodes, higher amounts of SWS 1 and REM sleep, and a shorter latency of this stage. These sleepwakefulness alterations in H mice are consistent with the data obtained in various depression models in the rat (Adrien et al, 1991;Dugovic et al, 2000;Nestler et al, 2002;Shiromani et al, 1988). Furthermore, they are reminiscent of sleep impairments observed in depressed patients, notably the sleep fragmentation, the shift towards lighter sleep stages, and the enhanced REM sleep pressure (Benca, 2000;Gillin et al, 1991).…”

“…For both males and females, H mice exhibited significantly lower levels of wakefulness (ANOVA: F 1,220 ¼ 23.0, po0.001) and greater amounts of REM sleep (F 1,220 ¼ 21.2, po0.001) and SWS 1 (F 1,220 ¼ 78.0, po0.001) across the 24 h, compared to NH mice ( Figure 2, Table 2). SWS 2 was increased at the beginning of the dark period (Figure 2) but represented in the whole a smaller proportion of total sleep in H than in NH mice ( (Dugovic et al, 2000).…”

“…Sleep fragmentation was assessed by calculating the mean duration of SWS 2 episodes as well as the number of wake bouts (Dugovic et al, 2000). The mean values were expressed as minutes7SEM for each line of mice, and significance was tested by performing a two-way ANOVA with repeated measures over time.…”

“…Studies of sleep patterns in these various models might help to elucidate the mechanisms underlying the relationship between depression and sleep abnormalities. To date, these aspects have only been studied in a few of these models, and mostly in rats (Adrien et al, 1991;Dugovic et al, 2000;Overstreet, 1993;Willner, 1990). We recently developed a line of mice selected from its long duration immobility in the tail suspension test ('Helpless' -H), compared to 'non-Helpless' (NH) mice which exhibited short duration immobility in the test (El Yacoubi et al, 2003).…”

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

“…Interestingly, others have tagged the WKY rats as a possibly stress-sensitive strain (Pare and Redei 1993;Pare and Kluczynski 1997). Numerous reports have indicated that the WKY rats display high anxiety and low locomotion reactivity compared with other strains (Pare 1992a(Pare , b, 1993(Pare , 1994Dugovic et al 2000). Likewise, the WKY have been proposed as an animal model of depressive behavior because they consistently demonstrate exaggerated behavioral and physiologic responses to stress in a variety of situations when compared with other strains (Pare 1993(Pare , 1994.…”