Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common childhood psychological disorders, occurring in as many as 3-5% of children. The symptoms of ADHD, including inattention, restlessness, impulsivity, and hyperactivity, often lead to significant difficulties in functioning. Dysfunction of central dopaminergic and noradrenergic systems is thought to play a major role in producing this impairment. A recent clinical study by members of our group provides preliminary evidence that nicotine treatment ameliorates the deficits in behavioral inhibition in adolescents suffering from ADHD. Interestingly, adolescents with ADHD are twice as likely to become cigarette smokers and tobacco users as those without ADHD, a trend that continues into adulthood. The positive effects of nicotine on cognitive processing and inhibition may contribute to the higher risk of chronic tobacco use/abuse. At the present time, the reasons underlying the vulnerability of individuals with ADHD to use/abuse tobacco are poorly understood, as are the neurobiological mechanisms by which nicotine exerts its beneficial effects. To fill this gap in the existing literature, this R21 application will develop a research partnership between existing basic and clinical investigators to explore the role of cholinergic systems in the cognitive and behavioral symptomatology of ADHD and possible links to substance abuse. Basic studies of the behavioral and neurobiological mechanisms of cholinergic involvement related to ADHD will have direct bearing on clinical research by 1) providing additional insight into the etiology of ADHD, 2) improving the characterization of behavioral and neurochemical deficits associated with this disorder, 3) guiding future drug development (e.g., cholinergic therapies), and 4) facilitating the identification of individuals who may be at high risk for substance abuse. Consistent with the recent recommendations of the National Advisory Mental Health Council Behavioral Science Workgroup (2000), the primary outcome of our collaboration will be the development of a coherent Translational Research Agenda to develop this area of research. In addition, the proposed activities will generate valuable preliminary data for subsequent full-scale studies and preparation of follow-up research applications (e.g., R01, R24).
