Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders

Amy F.T. Arnsten, Steven R. Pliszka

Research output: Contribution to journalReview articlepeer-review

172 Scopus citations

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 α2A-adrenoceptors and dopamine D1-receptors, respectively. Stimulant medications and atomoxetine appear to enhance PFC function through increasing endogenous adrenergic and dopaminergic stimulation of α2A-receptors and D1-receptors. In contrast, guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α2A- 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.

Original languageEnglish (US)
Pages (from-to)211-216
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume99
Issue number2
DOIs
StatePublished - Aug 1 2011

Keywords

  • Alpha-2A adrenergic receptors
  • Attention deficit/hyperactivity disorder
  • Catecholamines
  • Guanfacine
  • Norepinephrine
  • Prefrontal cortex

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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