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RESEARCH PRODUCT

Impact of type 2 diabetes on depressive-like phenotype and antidepressant response in mice

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Abstract at the 17th Annual Meeting of French Society of Pharmacology and Therapeutics, the 80th Annual Meeting of Society of Physiology, the 34th Pharmacovigilance Meeting, the 14th APNET Seminar and the 11th CHU CIC Meeting, 22-24 April 2013, Angers, France.; International audience; Evidence indicates that the prevalence of depression in diabetic subjects is higher than that in the general population. Despite these observations, the mechanisms underpinning the link between metabolic and psychiatric disorders are poorly understood. Moreover, it has been proposed that an impairment of glucose homeostasis may result in blunted antidepressant response to selective serotonin reuptake inhibitors (SSRI). To confirm and better understand the impact of type 2 diabetes (T2D) on the physiopathology and treatment of depression, this study evaluated the effects of a long-term (8 weeks) high fat diet (HFD) on depressive-like phenotype and SSRI response in mice. The results indicated that mice fed a HFD (protein 21% - fat 5%) exhibited a higher body weight (34,5±0.9 vs 28±0.6 g; p<0.001) and basal blood glucose level (180±4 vs 139±5 mg/dL; p<0.001) associated with a moderate insulin resistance compared to control mice fed a standard diet (STD: protein 20% - fat 45%). The alteration of these metabolic parameters, were accompanied by a high level of anxiety in HFD mice as shown by a decrease in the time spent in the anxiogenic areas (402±41 vs 701±50 sec. in the center of the arena; p<0.001 and 29±3 vs 42±6 sec. in the open arms; p<0.05) in the open-field and the elevated plus maze tests; respectively. Another symptom of depression such as helplessness reflected by a decreased immobility time in the tail suspension test was also unveiled in HFD compared to STD mice (120±12 vs 72±10 sec.; p<0.05). Finally, in the splash test measuring the time of grooming after the application of sweetened solution on the coat, this parameter was decreased in HFD compared to STD mice (95±7 vs 180±10 sec.; p<0.001). This result indicated a carelessness frequently observed in depressed patients. These data support the idea that T2D may precipitate depression. Experiments are in progress to test the antidepressant-like response of chronic administration of SSRIs in HFD and STD mice. This aspect is important for the "well-being" of diabetic-depressed patients. Indeed, an early and adapted psychiatric care may improve the efficacy of their anti-diabetic treatment by a better style of life and compliance.