SLEEP ANALYSIS IN A NEW MOUSE MODEL OF STRESS-INDUCED DEPRESSION: A PILOT STUDY

Strekalova T., *Cespuglio R., *Valatx J-L., Spanagel R., Bartsch D., Henn F., Gass P.
Center for Mental Health, J5 68159 Mannheim, Germany (stre@zi-mannheim.de)
*INSERM 480, Claude Bernard University, Lyon, Rockefeller av. 8, 69373, France

In order to establish a model of depression in mice, we subjected male C57BL/6 mice to a 4 weeks long stress procedure comprising rat exposure, restrained stress and tail suspension. This protocol led to a strong decrease in sucrose preference, a sign of anhedonia in rodents in a great majority of stressed animals. Mice that underwent a stress procedure, not accompanied by a decrease in sucrose preference, were considered as resistant to stress-induced anhedonia. These mice were employed as an internal control for the effects of chronic stress since they were exposed to the same stresses as the animals developing an anhedonic state. Behavioral analysis performed after terminating the stress procedure showed that features of anhedonia and chronic stress can be clearly distinguished in our model. Anhedonia, but not chronic stress per se, is associated with key analogues of depressive symptoms such as increased floating in forced swimming and decreased exploration of novelty. Other behavioral changes, e.g., increased anxiety in the O-maze and locomotor alternations resulted from chronic stress independently from anhedonia.

We also investigated whether anhedonic state, in contrast to the effects of chronic stress, was accompanied by specific changes in sleep pattern. In depressive patients, REM sleep is characterized by specific changes, e.g. decreased latency, increased amount during the first part of the night and flattening of the circadian component. Therefore, 1 week after chronic stress procedure, anhedonic, resistant and control mice were implanted with electroencephalographic (EEG) and electromyographic (EMG) electrodes. After 7 recovery days, polygraphic recordings were started in all animals. In order to reinstate anhedonia, stressed groups were submitted to an additional stress session during 5 days (anhedonic status was verified by the sucrose test). In the above experimental conditions, REM sleep latency was lengthened and state duration significantly elevated during the active phase (dark period) in anhedonic versus control and resistant animals. Circadian parameters were also modified. Thus, stress-induced anhedonia, contrary to stress exposure alone, seems to correlate with some sleep pattern alterations reported in depressive patients. Additional studies are required for a more detailed analysis of the sleep changes occurring in our animal model.