Opioid-Induced Dysregulation of BDNF Signalling: A Study of Acute, Sub-Chronic, and Chronic Exposure in a Rodent Model

Abstract

Brain-derived neurotrophic factor (BDNF) is a critical regulator of neuronal survival, synaptic plasticity, and cognitive function, making it a key biomarker in understanding the neurobiological impact of opioid exposure. This study investigated the effects of opioids (codeine and tramadol) on brain-derived neurotrophic factor (BDNF) levels in male Wistar rats. A total of 75 male Wistar rats (120-140g) were used for the study in acute, sub-chronic and chronic phases, using 25 rats for each phase. In each phase, 25 male Wistar rats were divided into 5 groups of 5 animals each. Group 1 served as the control and received distilled water, groups 2 and 3 were treated with tramadol at 20 and 60 mg/kg, respectively, while groups 4 and 5 were supplemented with codeine at 10 and 30 mg/kg, respectively. Treatment by oral gavage lasted for 14, 28 and 56 days for the acute, sub-chronic and chronic studies, respectively. Serum and hippocampal BDNF assays were analysed following standard laboratory protocols. Results showed dose and time-dependent significant reductions (p < 0.05) in BDNF levels across all treatment groups compared to controls, with the most pronounced decreases observed in codeine 30mg/kg and tramadol 60mg/kg groups. These findings suggest that prolonged opioid exposure disrupts neurotrophic signalling, potentially contributing to neurodegenerative conditions.