Abstract Backgrounds: Methadone and morphine are frequently used as pain relievers. Although they can be used to substitute opioids such as heroin, they can be addictive. Abuse of these substances might lead to memory loss and anxiety. Materials and Methods: 36 male rats weighing between 200 gr were divided into 6 groups. Each group contained 6 rats. The first group received no medicine. The second group received normal saline and consider as a positive control. The third group received methadone in high dosage, the fourth group received a low dosage of methadone. The fifth group received morphine in high dosage and the last group received morphine in low dosage for 30 days subcutaneously. After treatment, shuttle box and Plus Maze tests were used to evaluate brain activity and anxiety. Rats were sacrificed after being anesthetized with xylocaine and ketamine injection. The Gfap gene expression was evaluated after the hippocampus was harvested. Total RNA was extracted, cDNA was synthesized, and the expression level was determined using the RT-qPCR method. Results: Behaviour evaluation revealed a sizable reduction in brain activity and elevated anxiety in all groups in comparison with control groups. The groups who were treated with methadone and morphine in high dosage showed a severe condition. Gene evaluation discovered identical results and it is demonstrated Gfap expression reduced in methadone and morphine consumer groups. Conclusion: Taking methadone and morphine even at low doses can disrupt basic mental mechanics. One of the outcomes of methadone and morphine is a reduction in brain activity and increased tension even though reduction of Gfap expression. Gfap is a class-III intermediate filament and acts throughout the development of the central nervous system and distinguishes astrocytes from other glial cells. This study discovered that methadone and morphine consumption can disrupt Gfap expression and cause mental disorders.
