Effects of chronic oxycodone administration on the rat's hippocampus: Behavioral and histopathological studies

Oxycodone is a potent opioid frequently prescribed for pain management and is associated with a high tendency for abuse. This study investigated the impact of chronic oxycodone use on hippocampal structure and function in rats. Twenty-four adult male albino rats were randomly divided into a control group (n = 12) and an oxycodone-treated group (n = 12), receiving oral oxycodone (15 mg/kg) daily for 30 days. Behavioral tests included the Y-maze, shuttle box, elevated plus maze, tail suspension tests, Morris water maze and Barnes test. Immunohistochemical analysis was performed to evaluate the expression of Ki67 and caspase-3 in the hippocampus. Glial morphology and distribution were assessed using GFAP and Iba-1 antibodies, and the spatial distribution of neurons was analyzed using Voronoi tessellation. Chronic administration of oxycodone significantly reduced spatial working memory and increased depressive-like behavior. No significant changes were observed in anxiety-like behavior, spatial memory or long-term memory. Immunohistochemical analysis revealed a significant decrease in Ki67 expression and an increase in caspase-3 expression in the oxycodone-treated group. Oxycodone administration also led to an increase in astrogliosis, although astrocyte morphology was not significantly altered. Neuronal distribution analysis of the hippocampus in the oxycodone group showed a more regular distribution pattern in the pyramidal layer, with a significant increase in the proportion of larger Voronoi polygons. Chronic oxycodone administration reduces hippocampal neurogenesis, increases apoptotic activity, and affects neuronal distribution, resulting in behavioral alterations in rats. These findings highlight oxycodone's broader neurobiological impacts and the significance of tailored therapeutic techniques to reduce its effects on brain function.