Considering noradrenergically mediated facilitation of sensory signal processing as a component of psychostimulant-induced performance enhancement

Prescription stimulants are used to treat attention deficit hyperactivity disorder (ADHD). Psychostimulants are also used off-label by non-ADHD patients as performance-enhancing agents across academic, occupational, athletic, and social settings. Extensive work has focused on the reinforcing effects and abuse liability of psychostimulants, but understanding the mechanisms through which these agents regulate neural circuit functions that govern cognitive and sensorimotor processes to result in their performance-enhancing effects has received less attention. Optimal detection of sensory information within complex, dynamic environments is critical for appropriate decision making and executive actions. As such, overall performance enhancement may significantly rely on improvements in the processing of incoming sensory stimuli. Psychostimulants enhance catecholamine neurotransmission through the blockade of dopamine and norepinephrine (NE) reuptake transporters. The ascending locus coeruleus (LC)-NE system regulates behavioral state and modulates state dependent transmission of sensory signals. LC stimulation and local administration of NE to sensory processing areas of the brain can change the dynamics of both cellular and circuit activity in response to incoming sensory information. Here we explore the LC-NE system's neuromodulatory role in altering sensory signal processing as a plausible mechanism through which psychostimulant agents amplify physiological responses to important sensory stimuli as a component of their performance-enhancing effects in both ADHD patients and otherwise healthy individuals. We further consider sensory enhancement as a desirable outcome that has not previously been explored as an element of therapeutic efficacy, as well as added motivation for otherwise healthy individuals to engage in off-label self-administration of psychostimulant drugs.