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Early Exposure to Stimulants as a Risk Factor for Substance Abuse

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The periods of adolescence and early adulthood are times of risk for the development of addiction and substance abuse disorders. Although there are many risk factors that may increase vulnerability, including family history, genetic background, psychiatric and behavioral disorders, and peer pressure, one important factor is early exposure to drugs during childhood. This has raised concerns about the use of stimulant medications for childhood psychiatric disorders such as attention deficit hyperactivity disorder (ADHD). Most of the studies conducted in children and adults with ADHD have suggested that medication with methylphenidate or amphetamine has either no effect or can be protectivefrom substance abuse disorders. However, it is impossible to distinguish between the effects of the stimulants and ADHD itself. Given that these stimulants can produce dramatic neuroadaptations in the dopamine system and disruptions of dopamine systems may increase vulnerability to drug abuse, the question of long-term adverse consequences of stimulant medication still remains. The overallpurpose of this application is to address this question in a non-human primate model. Juvenile rhesus monkeys (approximately 20 mos at the start of the study) will be exposed to oral doses of methylphenidate or amphetamine or placebo for one year. Dopamine function as assessed with positronemission tomography, brain development assessed with magnetic resonance imaging, and markers of physical growth and social development will be measured before treatment commences, at the end oftreatment and 3 months after cessation of the medication regimen. Finally, we will assess the reinforcing efficacy of the psychostimulant cocaine once monkeys enter adolescence. These studies are not intended to evaluate all of the potential consequences of stimulant medication in childhood for the treatment of ADHD, but to answer the question of whether stimulant exposure can predispose adolescents to the development of substance abuse disorders.
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