Drug addiction is a serious social problem and continues to cause an enormous financial burden on society. It is characterized by drug dependence, tolerance, sensitization and craving. The available treatments remain inadequate for drug abusers, and addiction relapse rates vary depending on the substance being abused. Therefore, an improved understanding of the biological changes underlying the process of drug addiction and abstinence will be important for developing more effective treatments. Previous studies have demonstrated that metabolism and endocrine systems are actively involved in the process of long-lived behavioral abnormalities associated with addiction. In addition, drug addiction is associated with many neurotoxic effects, which are often associated with oxidative stress. Mitochondria play an important role in cellular metabolism, energy production, and also act as a primary source of reactive oxygen species (ROS) production that contribute to cell damage and apoptosis. Cytoplasmic and mitochondrial enzymes have been identified as potential markers associated with drug dependence. Chronic morphine treatment also results in mitochondria-dependent apoptosis and mitochondrial dysfunction. Mitochondrial function is strongly associated with the amount and quantity of mtDNA. High level of ROS production causes oxidative damage of mtDNA, which ultimately leads to a wide array of multisystem disorders, particularly affecting the energy-dependent central nervous system. Mitochondria are actively involved in regulation of synaptic plasticity, and their dysfunction may underlie neurological changes in addiction. Nevertheless, the mechanisms that underlie potential mtDNA alterations observed in drug-addicted individuals and neuroplasticity have not been fully elucidated. Because mitochondrial abnormalities have been associated with opiate addiction, we examined the effect of morphine on mtDNA levels in heroin addicts, rat model of addiction and in cultured cells. We found that heroin addicts had a lower level of mtDNA copy number in the peripheral blood (P=0.0248), and a higher level of mtDNA damage compared to healthy individuals (P=0.006). During the rehabilitation of drug abusers after drug detoxification for 3 months, we observed a significant increase of mtDNA content (P<0.0001) and a decrease of mtDNA damage (P=0.036) compared to those at the initiation of drug withdrawal.
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