Effect of chronic mild stress on circadian rhythms in the locomotor activity in rats.

The purpose of this study was to assess whether the chronic mild stress (CMS) procedure, as a realistic animal model of depression, affects the rhythms of the locomotor activity in rats. Rhythm parameters (period, mesor, amplitude, acrophase, and percent rhythm) were estimated from the best-fitted cosine function curves. Period is the length, mesor is the mean level, amplitude (A) is the extent, acrophase is the timing of the rhythm; percent rhythm represents the variability estimated by the cosine regression and expressed as a percentage of the total variability of raw data. The animals were kept on the 12 L : 12 D cycle during 13 weeks of the experiment and subjected to CMS for first 4 weeks. In week 5 the rats were under the constant light for 24 h a day (LL), and in week 9, under the constant darkness (DD). In LD 12:12 CMS decreased the activity in the dark phase by approximately 50% (p < 0.01) and did not change the activity in the light phase, resulting in a drop of the 24 h activity by about 40% in comparison to controls. The amplitude of diurnal variations of the activity was highly statistically different from zero at p(A = 0) < 0.0001, and the percent rhythm was in range of 40-75% in both the CMS and control groups. The mesor and the amplitude of the diurnal rhythm (with a period of 24 h) in the CMS rats were significantly (p < 0.001) lower than those in the control. In LL, the activity of both groups was diminished about 50% during the subjective dark phase. On the other hand, in the subjective light phase the activity of CMS rats only was diminished. The percent rhythm for the CMS and control rats was 30 and 58%, respectively, and values of mesor, amplitude, and acrophase for both groups were highly statistically different. In DD, the activity in the CMS group was statistically significantly lower in both the subjective dark and light phases. In contrast to the results from LL, the cosine curves from DD were similarly shifted in relation to the subjective light-dark cycle. After a restoration of the LD cycle the levels of the 24-h activity of both groups became equal in the 13th week, but the light and dark phase differences between the groups were still statistically significant (p < 0.05). The present results indicate that CMS exerts distinct and prolonged disturbances of the diurnal and circadian rhythms of the locomotor activity in the rats.