Substance abuse disorders (SUDs) present a major public health problem in the U.S. Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent psychiatric disorder that emerges during childhood and that has been repeatedly associated with increased rates of later substance use and SUDs. This disorder is most commonly and effectively treated with stimulant medications, substances which themselves have abuse potential. This fact has engendered concern in the scientific and lay communities that childhood treatment with stimulants may put patients at increased risk for later substance use. Much of this concern has stemmed from the fact that these medications exert direct effects on the human neural reward circuitry, the same systems implicated in SUDs, and from animal studies suggesting that exposure to stimulants mediates behavioral sensitization to the effects of subsequent administration as well as increased risk for the subsequent development of addictive behaviors. However, the extant human and animal research literature is equivocal regarding the impact of stimulant treatment on the propensity to later SUD and, at present, minimal data are available on the long-term neural and behavioral consequences of early exposure to MPH in humans. No human study has examined whether brain functioning is altered as a result of early stimulant exposure. This is important because data suggest that low premorbid mesolimbic DA activity confers risk for later substance use, and several fMRI studies have differentiated substance abusers and controls on patterns of activation and neurotransmission in brain regions associated with reinforcement learning. The proposed study will examine differential patterns of neural activation, as measured using fMRI, in a network of neural regions associated with processing of reward contingencies and cognitive control, including ventral and dorsal striatum, prefrontal cortex, amygdala, and anterior cingulate gyrus, in adults with childhood ADHD who did and did not receive treatment with stimulants. While the proposed I/START will be mainly exploratory in nature, the aim is to determine whether functional activity in treated and untreated individuals look different in key brain areas that have been empirically linked to the propensity for substance use and abuse. PUBLIC HEALTH RELEVANCE: There is current concern that the use of stimulant medications such as Ritalin in the treatment of children with Attention-Deficit Hyperactivity Disorder (ADHD) increases the likelihood of children to later develop substance use disorders;however, data from the research literature regarding this issue are inconclusive. The primary aim of this I/START is to examine differences in human brain systems that govern reward-related learning (i.e., those compromised in addiction) associated with long-term treatment with stimulant medications. This study will capitalize on the ability of functional magnetic resonance imaging (fMRI) to image these regions of the brain with exquisite spatial resolution, and will garner preliminary data regarding changes in neural functioning that may or may not be associated with a greater propensity for later substance abuse.