Towards a mouse model of depression : a psychoneuroendocrine approach

Dalm, S. (2012)

Doctoral Thesis

Chronic stress is considered a vulnerability factor for depression. A key symptom is anhedonia; a reduced response to positive stimuli. Drugs are effective for only 20-40% of the patients and new drugs are urgently needed. The objective of the research was to develop a mouse model of depression that would express anhedonia, induced by chronic stress. Mice were repeatedly exposed to the non-physical presence of a rat. Alterations in stress system activity were measured. Anhedonia was assessed by studying the behavioral response to positive stimuli. As a potential therapeutical approach we assessed reward expectation, and studied the effect of repeated administration of mifepristone (glucocorticoid receptor antagonist), directly targeting stress system regulation. Our model induced changes in the sensitivity of the reward system that contributed to cognitive impairments underlying anhedonia. The effects could partially be restored by additional reward. Mifepristone in na_ve mice suppressed stress system activity, which could indicate a similar direction of effects in stressed mice if provided. Concluding, our chronic stress mouse model induces anhedonia. The new methodology to reduce stress by either providing additional positive stimuli or mifepristone, increases the well being of the mice and may prove a new drug target to treat depression in humans.

• Inhibition
• Mice
• Mifepristone
• Learning and memory
• Corticosterone
• Anhedonia
• Stress

• All authors: Dalm, S.
• Supervisor: Kloet, E.R. de; Oitzl, M.S.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2012-11-21
• ISBN (print): 9789088915116