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Effects of voluntary imipramine intake via food and water in paradigms of anxiety and depression in naive mice

Translational Neuroscience and Clinics 2016年第3期2卷 172-182,149页

作者： Joao Pedro Costa-Nunes anastassia bakhmet Margarida Araújo-Correia Andreia Barbosa Valenca Tatyana Strekalova Harry W.M.Steinbusch School for Mental Health and Neuroscience Maastricht University Center for Neuroscience and Cell Biology Universidade de CoimbraFaculdade de MedicinaRua Larga Centro de Biologia Ambiental Faculdade de Ciências da Universidade de Lisboa Department of Human Anatomy Moscow State Medical University Centro de Estudos de Doencas Crónicas(CEDOC) Edifício CEDOCⅡRua Camara Pestana Centro Interdisciplinar de Investigacao em Saúde Animal(CIISA) Faculdade de Medicina VeterináriaAlameda da Universidade Técnica

Objective: We sought to investigate the efficacy of oral dosing in mice with imipramine(7mg/kg/day) via water or in food pellets, and to compare its effects in the paradigms of learned helplessness, locomotion, hedonic state, and anxiety. Methods: Water and food consumption were measured to determine daily imipramine dosage in C57BL/6N mice. Next, baseline scores for O-maze, dark/light box, and sucrose tests were measured. Mice were then subjected to a 4-week treatment of voluntary ingestion of drinking water or food pellets containing imipramine. Lastly, all groups were subjected to novel cage, open field, O-maze, dark/light box, sucrose test, and forced swim test to assess the effects of the treatment. Results: In na?ve mice, imipramine delivered via food, induced a reduction of total floating and increased latency in the forced swim test, i.e., antidepressant-like effects. No other significant effects were found. Dosing with water did not change behavior in the forced swim, sucrose preference test, anxiety, or locomotor paradigms, but increased exploration in the novel cage. Conclusions: Voluntary ingestion is an effective method of chronic dosing with imipramine in na?ve mice. Delivery of imipramine with food pellets elicits antidepressant-like effects in the forced swim test, with no effects on anxiety, locomotion, or preference behaviors. In contrast, no such effects were observed with treatment via drinking water, suggesting that a higher dose may be required. Our work argues for a broader use of oral delivery using food-treated pellets, in small rodent models of pre-clinical depression. It may substantially improve animal welfare and overcome potential confounds in translational research, which are frequently associated with adverse chronic invasive pharmacotherapies.

关键词： pre-clinical models depression anxiety oral dosing animal welfare

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