title: Catecholamine influences on prefrontal cortical function: relevance to treatment of attention deficit/hyperactivity disorder and related disorders.
abstract: The primary symptoms of attention deficit/hyperactivity disorder (ADHD) include poor impulse control and impaired regulation of attention. Research has shown that the prefrontal cortex (PFC) is essential for the "top-down" regulation of attention, behavior, and emotion, and that this brain region is underactive in many patients with ADHD. The PFC is known to be especially sensitive to its neurochemical environment; relatively small changes in the levels of norepinephrine and dopamine can produce significant changes in its function. Therefore, alterations in the pathways mediating catecholamine transmission can impair PFC function, while medications that optimize catecholamine actions can improve PFC regulation of attention, behavior, and emotion. This article reviews studies in animals showing that norepinephrine and dopamine enhance PFC function through actions at postsynaptic α(2A)-adrenoceptors and dopamine D1-receptors, respectively. Stimulant medications and atomoxetine appear to enhance PFC function through increasing endogenous adrenergic and dopaminergic stimulation of α(2A)-receptors and D1-receptors. In contrast, guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α(2A)-receptors in the PFC, strengthening network connectivity. Stronger PFC regulation of attention, behavior, and emotion likely contributes to the therapeutic effects of these medications for the treatment of ADHD.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA. amy.arnsten@yale.edu
authors.forename: Amy F T
authors.initials: AF
authors.lastname: Arnsten
authors.forename: Steven R
authors.initials: SR
authors.lastname: Pliszka
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology*; D002395:Catecholamines / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology; D016316:Guanfacine / Q000494:pharmacology; D006801:Humans; D008959:Models, Neurological; D009638:Norepinephrine / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology*; D011437:Propylamines / Q000494:pharmacology; D017983:Receptors, Catecholamine / Q000187:drug effects / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058647:Adrenergic alpha-2 Receptor Agonists; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D011437:Propylamines; D017983:Receptors, Catecholamine; D016316:Guanfacine; D000069445:Atomoxetine Hydrochloride; D004298:Dopamine; D009638:Norepinephrine