Dexamphetamine-induced Reduction of P3a and P3b in Healthy Participants

The reduced P3 is one of the most robust deficits involved in schizophrenia. Previous research with catecholaminergic agonists or releasers such as amphetamines have used doses too small to adequately demonstrate an effect on P3. In this study, we gave 0.45 mg/kg dexamphetamine to healthy volunteers (final n = 18) using both auditory and visual three-stimulus P3 procedures. Dexamphetamine significantly reduced P3 amplitudes to auditory target, rare non-target and standard stimulus amplitudes. The reduction in auditory P3 induced by dexamphetamine was proportional across stimulus types to placebo P3 values. There were no effects of dexamphetamine on visual P3. We demonstrate a reduced auditory P3 similar to that seen in schizophrenia and other psychotic illnesses. This possibly reflects a common pathology which is hypothesized within the P3 literature to be related to attention and working memory. Differences between auditory and visual P3 modulation may be related to regional variations in catecholamine or specifically dopamine receptor densities. One specific auditory P3 generator is the superior temporal cortex, an area with dopamine D(2) receptor enriched bands. This is contrasted with visual specific generators, such as the inferior temporal cortex and superior parietal cortex, which do not have these enriched bands.