Methamphetamine induces DNA damage in specific regions of the female rat brain

• Published in: Clinical and experimental pharmacology & physiology 2015-06, Vol.42 (6), p.570-575
• Main Authors: Johnson, Zane, Venters, Jace, Guarraci, Fay A, Zewail-Foote, Maha
• Format: Article
• Language: English
• Subjects: Animals; Brain - drug effects; Brain - metabolism; comet assay; Corpus Striatum - drug effects; Corpus Striatum - metabolism; DNA damage; DNA Damage - drug effects; DNA Damage - physiology; DNA strand breaks; Female; methamphetamine; Methamphetamine - toxicity; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; rat brain cells; Rats; Rats, Long-Evans; Reactive Oxygen Species - metabolism
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.12404

Summary Methamphetamine (METH) is a highly addictive psychostimulant that has been shown to produce neurotoxicity. Methamphetamine increases the release of dopamine by reversing the direction of monoamine transporter proteins, leading to the formation of reactive oxygen species in the brain. In this study, we examined the effect of METH on DNA damage in vivo using the single cell gel electrophoresis assay (comet assay) under two different conditions. Rats treated with multiple doses of METH (10 mg/kg × 4) showed significant levels of DNA damage in the nucleus accumbens and striatum, both dopamine‐rich areas. In contrast, a single dose of METH did not lead to significant levels of DNA damage in any of the dopamine‐rich brain regions that were tested. Overall, the results of our study demonstrate that METH produces greater oxidative DNA damage in brain areas that receive greater dopamine innervation.