Cholinergic Effects on Inhibition and Delay in ADHD

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Impulsivity is a central characteristic of Attention-Deficit/Hyperactivity Disorder (ADHD). Laboratory studies support this deficit in ADHD using a variety of tasks measuring behavioral inhibition, motivation, reward sensitivity and executive functioning. Recent evidence suggests that two models of the cognitive underpinnings of impulsive behavior, the behavioral inhibition model (Bl) and the delay aversion (DA) model, contribute independently to ADHD symptoms. Dysfunction of central dopaminergic and noradrenergic systems are thought to be important in the behavioral symptoms of ADHD. Interestingly, the cholinergic system, known to be important in attention, has been understudied in ADHD. Acute nicotine administration ameliorates the deficits in behavioral inhibition in ADHD suggesting cholinergic modulation of this important behavioral deficit. Also, adolescents with ADHD are twice as likely to become regular tobacco users as those without ADHD, a finding that continues into adulthood. I believe that the positive effects of nicotine on behavioral inhibition may extend to other important cognitive processing (including delay aversion) and that these effects may contribute to the higher risk of chronic tobacco use/abuse in these adolescents and adults. Very little is currently known about the integrity of the cholinergic system in ADHD or how self administration of nicotine may affect the cognitive symptoms of ADHD. In addition, we do not know if the finding that nicotine improves behavioral inhibition is specific to ADHD or extends to controls with normal neurochemical functioning. The specific aim of this proposal is to address these gaps in the literature by more fully examining the effects of nicotinic cholinergic stimulation in patients with ADHD and a non-ADHD control group on key cognitive deficits in ADHD (delay aversion and behavioral inhibition).