Research Paper Volume 12, Issue 11 pp 10147—10161
Chronic polypharmacy impairs explorative behavior and reduces synaptic functions in young adult mice
- 1 Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Solna, Sweden
- 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- 3 Kolling Institute, Royal North Shore Hosptial and University of Sydney, Clinical Pharmacology and Aged Care, Sidney, Australia
- 4 Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden
Received: February 5, 2020 Accepted: April 28, 2020 Published: May 22, 2020https://doi.org/10.18632/aging.103315
How to Cite
Copyright © 2020 Eroli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
A major challenge in the health care system is the lack of knowledge about the possible harmful effects of multiple drug treatments in old age. The present study aims to characterize a mouse model of polypharmacy, in order to investigate whether long-term exposure to multiple drugs could lead to adverse outcomes. To this purpose we selected five drugs from the ten most commonly used by older adults in Sweden (metoprolol, paracetamol, aspirin, simvastatin and citalopram). Five-month-old wild type male mice were fed for eight weeks with control or polypharmacy diet. We report for the first time that young adult polypharmacy-treated mice showed a significant decrease in exploration and spatial working memory compared to the control group. This memory impairment was further supported by a significant reduction of synaptic proteins in the hippocampus of treated mice. These novel results suggest that already at young adult age, use of polypharmacy affects explorative behavior and synaptic functions. This study underlines the importance of investigating the potentially negative outcomes from concomitant administration of different drugs, which have been poorly explored until now. The mouse model proposed here has translatable findings and can be applied as a useful tool for future studies on polypharmacy.