Nieuwenhuis and Aston-Jones (2005) reviewed studies suggesting that P3 reflects activity in the locus coeruleus–norepinephrine system. Evidence for the role of the noradrenergic neurotransmitter system in modulating P3 was provided by the finding of opposing effects of α2 noradrenergic agonists and antagonists on the frontal P3a (Turetsky and Fein, 2002). The α2 antagonist yohimbine, which has anxiogenic effects, increased P3a amplitude in healthy adults, whereas the α2 agonist clonidine decreased P3a amplitude. The P3b component was not, however, affected by either noradrenergic agent. They suggest that norepinephrine enhances the physiological processes underlying the evaluation of novelty and selective attention to potentially important stimuli. The P3a or novelty decrement in depressed patients may therefore be a physiologic marker of a norepinephrine deficiency, which is thought to characterize at least a subgroup of depressed patients (Schildkraut, 1974). However, Polich (2007) reviewed evidence supporting the hypothesis that P3a is related to frontal attention mechanisms mediated by dopaminergic activity, whereas P3b is related to temporoparietal activity mediated by the norepinephrine system. Although further research on the neurotransmitter systems mediating P3 is needed, the widespread
