Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function

- Prefrontal cortical (PFC) dysfunction underlies most neuropsychiatric disorders.
- Pharmacological treatments optimize catecholamine signaling at PFC α2 and D1 receptors.
- These receptors improve PFC circuit function via actions of select intracellular pathways.
- Low doses of psychostimulants elevate catecholamine signaling preferentially in the PFC.
- Higher, abuse-related doses of psychostimulants activate catecholamines outside the PFC.

Multiple psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), are associated with prefrontal cognitive dysfunction. The catecholamine neurotransmitters, norepinephrine and dopamine, are key modulators of prefrontal cognition. Moreover, pharmacological treatments for prefrontal dysfunction target catecholamines. Recent studies identify neurocircuitry, receptor mechanisms and intracellular pathways involved in catecholamine modulation of prefrontal cognition. Consistent with these observations, additional research identifies a pivotal role of prefrontal catecholamines in the cognition-enhancing effects of all approved pharmacological treatments for ADHD. Combined, this research suggests the clinical efficacy of ADHD medications involve catecholamine receptor mediated modulation of specific intracellular pathways and ion channels that strengthen PFC circuit function. Novel medications targeting different components of these pathways may result in improved treatments of PFC cognitive dysfunction.