Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression

• Main Authors: Flavie eDarcet, Indira eMendez-David, Laurent eTritschler, Alain M Gardier, Jean-Philippe eGuilloux, Denis Joseph David
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2014-05-01
• Series: Frontiers in Behavioral Neuroscience
• Subjects: Corticosterone; Depression; Associative Memory; recognition memory; cognitive impairments; anxiety/depression model
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fnbeh.2014.00136/full

Cognitive disturbances are often reported as serious incapacitating symptoms by patients suffering from major depressive disorders. Such deficits have been observed in various animal models based on environmental stress.<br/>Here, we performed a complete characterization of cognitive functions in a neuroendocrine mouse model of depression based on a chronic (4 weeks) corticosterone administration (CORT). Cognitive performances were assessed using behavioral tests measuring episodic (novel object recognition test, NORT), associative (one-trial contextual fear conditioning, CFC) and visuo-spatial (Morris water maze, MWM; Barnes maze, BM) learning/memory. Altered emotional phenotype after chronic corticosterone treatment was confirmed in mice using tests predictive of anxiety or depression-related behaviors.<br/>In the NORT, CORT-treated mice showed a decrease in time exploring the novel object during the test session and a lower discrimination index compared to control mice, characteristic of recognition memory impairment. Associative memory was also impaired, as observed with a decrease in freezing duration in CORT-treated mice in the CFC, thus pointing out the cognitive alterations in this model. In the MWM and in the BM, spatial learning performance but also short-term spatial memory were altered in CORT-treated mice. In the MWM, unlike control animals, CORT-treated animals failed to learn a new location during the reversal phase, suggesting a loss of cognitive flexibility. Finally, in the BM, the lack of preference for the target quadrant during the recall probe trial in animals receiving corticosterone regimen demonstrates that long-term retention was also affected in this paradigm. <br/>Taken together, our results highlight that CORT-induced anxio-depressive-like phenotype is associated with a cognitive deficit affecting all aspects of memory tested.