Many models, such as chronic mild stress, chronic stress or chronic corticosterone injections are used to induce depression associated with cognitive deficits. However, the induction period in these different models is still long and face constraints when it is short such as in the chronic mild stress done in a minimum period of 21 days. This study aimed to characterize a model of depression with early onset cognitive deficit. 14 days combined chronic injection of corticosterone followed by 2 h restraint stress using a restrainer was used to induce depression with early cognitive deficit onset. The forced swim test, sucrose test and plasma corticosterone concentration were used to assess depression-like characteristics. The Morris water maze, novel object recognition task, as well as hippocampal acetylcholinesterase activity were used to assess cognitive deficit. The combined corticosterone injection + chronic restraint stress group presented with marked depression-like behaviour and a higher plasma corticosterone concentration compared to corticosterone injection alone and restraint stress alone. It also showed an alteration in the learning process, memory deficit as well as increased acetylcholinesterase activity compared to corticosterone injection and restraint stress alone groups. These findings suggest that the combined corticosterone administration and chronic restraint stress can be used not only as an animal model for severe depression, but also for depression with early onset cognitive deficit.

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Background: Major Depressive Disorder is a common mental illness characterized by persistent low mood, cognitive impairment, anhedonia, weight gain, or loss and several other symptoms, ranging from psychomotor to cognitive impairments. Commonly available antidepressants show side effects and limited efficacy; therefore, an alternative is to be considered. Capparis sepiaria (Capparaceae) is a plant used in traditional medicine to treat mental disorders. The aim of this study was to investigate possible antidepressant-like effects of the aqueous lyophilizate of Capparis sepiaria in Wistar rats. Methods: Depressive-like behavior was induced using restraint stress for 14 days. The forced swimming test, the open field test, the sucrose preference test, body weight, and the food consumption were done to assess depressive-like behavior. On day 15 animals were sacrificed and the adrenal glands mass and the hippocampi were collected for Hypothalamo-pituitary-axis activity and oxidative stress markers assessment. Results: The aqueous lyophilizate of the root bark of Capparis sepiaria increased swimming time and decreased immobility time (p<0.001) in the forced swimming test and, increased sucrose consumption in the sucrose preference test (p<0.001). In the open field test, there was no difference in the number of lines crossed between groups. Chronic stress significantly increased adrenal weight (p<0.05) which was prevented by the aqueous lyophilizate of Capparis sepiaria at the dose 10 mg/kg. Chronic stress decreased food consumption and weight which was prevented by the aqueous lyophilizate of Capparis sepiaria. The lyophilizate increased the reduced glutathione (GSH) level (p<0.001), and Catalase activity (p<0.001), and decreased the malondialdehyde level (p<0.001) in the determination of some oxidative stress markers. Conclusion: These results suggest that the aqueous lyophilizate of the roots bark of C. sepiaria possesses antidepressant-like effects. Keywords: Depression; Capparis sepiaria; restraint stress; oxidative stress.

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