Research Paper Volume 13, Issue 11 pp 14729—14744
Long-term exposure to polypharmacy impairs cognitive functions in young adult female 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 Hospital and University of Sydney, Sydney, Australia
- 4 Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden
Received: February 10, 2021 Accepted: May 18, 2021 Published: June 2, 2021https://doi.org/10.18632/aging.203132
How to Cite
Copyright: © 2021 Francesca 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.
The potential harmful effects of polypharmacy (concurrent use of 5 or more drugs) are difficult to investigate in an experimental design in humans. Moreover, there is a lack of knowledge on sex-specific differences on the outcomes of multiple-drug use. The present study aims to investigate the effects of an eight-week exposure to a regimen of five different medications (metoprolol, paracetamol, aspirin, simvastatin and citalopram) in young adult female mice. Polypharmacy-treated animals showed significant impairment in object recognition and fear associated contextual memory, together with a significant reduction of certain hippocampal proteins involved in pathways necessary for the consolidation of these types of memories, compared to animals with standard diet. The impairments in explorative behavior and spatial memory that we reported previously in young adult male mice administered the same polypharmacy regimen were not observed in females in the current study. Therefore, the same combination of medications induced different negative outcomes in young adult male and female mice, causing a significant deficit in non-spatial memory in female animals. Overall, this study strongly supports the importance of considering sex-specific differences in designing safer and targeted multiple-drug therapies.