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Shannon Rae Klein,1 Kenneth Blum,2 Mark S Gold,3 Panayotis K Thanos1,4 1Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA; 2Center for Sports, Exercise, & Mental Health, Western University Health Sciences, Pomona, CA, 91766, USA; 3Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63130, USA; 4Department of Psychology, University at Buffalo, Buffalo, NY, 14203, USACorrespondence: Panayotis K Thanos, Tel +1 716 881-7520, Email thanos@buffalo.eduAbstract: Methylphenidate (MP) is a psychostimulant commonly prescribed for individuals with attention deficit hyperactivity disorder (ADHD) but it is also taken with and without a prescription for performance enhancement. Prior research has characterized the effects of MP on behavior, cognition, and neurochemistry. This exploratory review covers the uses of MP and examined the effects of MP on gene expression in the brain following exposure. Overall, MP causes a wide-spread potentiation of genes, in a region-specific manner; consequently, inducing neuronal alterations, such as synaptic plasticity and transmission, resulting in observed behaviors and affects. Monoamine neurotransmitters and post-synaptic density protein genes generally had a potentiating effect in gene expression after exposure to MP.Keywords: addiction, substance abuse, methylphenidate, gene expression, monoamine neurotransmitters postsynaptic density proteins, reward deficiency syndrome