FIGURE 2.

Actions of methylphenidate via catecholamines in prefrontal cortex. (A) Methylphenidate has greater effects on catecholamine levels in prefrontal cortex than in subcortical structures in rat brain. (B) Catecholamines have an inverted U dose response on prefrontal top-down control, where either too little or too much is detrimental to function. The beneficial effects of moderate norepinephrine levels are through high affinity, postsynaptic alpha-2A-AR, while the detrimental actions at high levels of norepinephrine release are through low affinity alpha-1-AR. In contrast, dopamine has both beneficial and detrimental actions through increasing engagement of D1R. PFC: prefrontal cortex, MSA: medial septal area, NAc: nucleus accumbens. Adapted from Berridge and Arnsten, 2013.⁵³