Central nicotinic cholinergic systems: A role in the cognitive dysfunction in Attention-Deficit/Hyperactivity Disorder?

Theories of the neurobiological basis of Attention-Deficit/Hyperactivity Disorder (ADHD) have largely focused on dysregulation of central dopaminergic function. However, other neurotransmitter systems may be implicated in specific cognitive deficits in ADHD. Interest in the potential involvement of nicotinic cholinergic systems in ADHD has arisen in part from the observation that adolescents and adults with ADHD smoke cigarettes at significantly higher rates than people without this disorder. In addition, several studies report that nicotine alleviates ADHD symptoms, and recent neuro-genetics studies indicate that cholinergic systems may be altered in persons with ADHD. In this review, we describe the evidence for a role of central nicotinic cholinergic systems in cognitive deficits in ADHD. We also propose mechanisms by which alterations in cholinergic function may contribute directly and/or indirectly to these deficits. Finally, we identify specific paradigms and models to guide future investigations into the specific involvement of nicotinic cholinergic systems in ADHD, possibly leading to the development of more effective pharmacotherapies for ADHD.