Environmental Enrichment and Metformin Combination Improves Cognitive Function through BDNF and HPA Axis in Chronically Stressed Rats
Abstract
INTRODUCTION: Chronic stress is a major global health issue linked to conditions such as anxiety, depression, and cognitive decline. In rodent studies, chronic immobilization stress (CIS) is commonly used to investigate the neuropsychological effects of prolonged stress, leading to behaviours such as anhedonia, anxiety, and depressive-like symptoms. An enriched environment (EE) provides physical, cognitive, and sensory stimulation, which promotes social interaction, supports brain development, and can enhance the effectiveness of pharmacological treatments, improving overall therapeutic outcomes. Metformin, commonly prescribed for type 2 diabetes, has antidiabetic effects and helps reduce oxidative stress, inflammation, and cell death in the brain, which may contribute to its neuroprotective properties. This study aims to evaluate the effectiveness of metformin, an enriched environment (EE), and its combination in alleviating anxiety and depression-like behaviours, memory impairments, and metabolic changes.
MATERIALS AND METHODS: Rats were exposed to chronic immobilization stress (CIS) for 2 hours per day over a period of 10 days, followed by 14 days of treatment with metformin (200 mg/kg) and 6 hours of daily exposure to an enriched environment (EE). Behavioural tests, including the open field test (OFT), elevated plus maze (EPM), sucrose preference test (SPT), and novel object recognition test (NORT), were conducted. After completing the behavioural assessments, the…
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