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Effect of Diamorphine on Spatial Learning and Memory and Mitochondrial Function of Male Rat Brain Publisher



A Moshtagh AINAZ ; M Mehdizadeh MARYAM ; G Hosseinifakhr GHODSIEH ; A Foroumadi ALIREZA ; M Baeeri MARYAM ; S Hassani SHOKOUFEH ; M Gholami MAHDI ; Z Emamgholipour ZAHRA ; O Sabzevari OMID ; R Hosseini ROHOLLAH
Authors

Source: Iranian Journal of Pharmaceutical Research Published:2025


Abstract

Background: Opioid abuse is a global crisis, with diamorphine being one of the most dangerous substances of abuse. Diamorphine is a major contributor to addiction and social issues. Objectives: This study aimed to investigate the impact of different doses of diamorphine on spatial learning and memory by examining its effects on brain mitochondria function. Methods: Four groups of nine rats were selected to receive diamorphine at doses of 1, 5, and 10 mg/kg, while one group received diamorphine solvent at a dose of 1 mL/kg. All treatments were given twice a day at 12-hour intervals for 10 days. The animals' memory performance was assessed using the Morris Water Maze test. Additionally, tests were conducted to measure ADP/ATP levels, mitochondrial reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), lipid peroxidation (LPO), and antioxidant function, including total thiol groups measurement (TTM), and ferric reducing antioxidant power (FRAP). Results: The results indicated that diamorphine at doses of 5 and 10 mg/kg significantly disrupted learning and spatial memory, as evidenced by changes in latency (P < 0.0001), distance (P < 0.0001), and time spent in the target quadrant (P < 0.0001). Diamorphine also negatively impacted mitochondrial function parameters, such as ROS levels (P < 0.0001), MMP (P < 0.0001), mitochondrial swelling (P < 0.0001), and ADP/ATP ratio (P < 0.0001). Furthermore, brain antioxidant capacity was compromised (P < 0.0001). Conclusions: This study on the mechanisms of brain damage induced by diamorphine showed that the harm arises from the impairment of mitochondrial function. This impairment leads to the generation of ROS, reduced antioxidant capacity, decreased MMP, and an elevated ADP/ATP ratio. © 2025 Elsevier B.V., All rights reserved.
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