Psychostimulants as Cognitive Enhancers: The Prefrontal Cortex, Catecholamines, and Attention-Deficit/Hyperactivity Disorder

• Published in: Biological psychiatry (1969) Vol. 69; no. 12; pp. e101 - e111
• Main Authors: Berridge, Craig W., Devilbiss, David M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2011
• Subjects: ADHD; Adrenergic Agonists - pharmacology; Adrenergic Agonists - therapeutic use; Animals; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - physiopathology; Catecholamines - metabolism; Catecholamines - physiology; Central Nervous System Stimulants - pharmacology; Central Nervous System Stimulants - therapeutic use; cognition; Cognition - drug effects; Cognition - physiology; dopamine; Humans; Monoamine Oxidase Inhibitors - pharmacology; Monoamine Oxidase Inhibitors - therapeutic use; Neurons - physiology; norepinephrine; prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Psychiatry; stimulants; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; norepinephrine; ADHD; stimulants; cognition; dopamine; prefrontal cortex
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2010.06.023

Psychostimulants exert behavioral-calming and cognition-enhancing actions in the treatment of attention-deficit/hyperactivity disorder (ADHD). Contrary to early views, extensive research demonstrates that these actions are not unique to ADHD. Specifically, when administered at low and clinically relevant doses, psychostimulants improve a variety of behavioral and cognitive processes dependent on the prefrontal cortex (PFC) in subjects with and without ADHD. Despite the longstanding clinical use of these drugs, the neural mechanisms underlying their cognition-enhancing/therapeutic actions have only recently begun to be examined. At behaviorally activating doses, psychostimulants produce large and widespread increases in extracellular levels of brain catecholamines. In contrast, cognition-enhancing doses of psychostimulants exert regionally restricted actions, elevating extracellular catecholamine levels and enhancing neuronal signal processing preferentially within the PFC. Additional evidence suggests a prominent role of PFC α 2 and D1 receptors in the behavioral and electrophysiological actions of low-dose psychostimulants. These and other observations indicate a pivotal role of PFC catecholamines in the cognition-enhancing and therapeutic actions of psychostimulants, as well as other drugs used in the treatment of ADHD. This information may be particularly relevant for the development of novel pharmacological treatments for ADHD and other conditions associated with PFC dysregulation.