Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers

Functional brain imaging is a powerful tool for examining the central nervous system (CNS) response to pharmacologic challenges. Amphetamine is of interest both because of its role as a stimulant of the dopaminergic system and because of its use to alter mood in mood-disordered patients, particularly in patients suffering from depression. In this study, we report the effects of oral D-amphetamine relative to placebo on regional cerebral blood flow (rCBF) measured by SPECT in healthy volunteers to characterize the normal CNS response to this primarily dopaminergic stimulant.

SPECT was used to assess changes in rCBF induced by amphetamine in 16 healthy volunteers. Subjects received placebo and then 0.4 mg/kg oral amphetamine in a fixed-order single-blind design and were imaged on a triple-head tomograph. Another six healthy volunteers received placebo at both times to assess normal rCBF variability. rCBF changes were assessed with a three-dimensional voxel-based analysis integrated into an automated coregistration system. Data were automatically normalized to whole-brain counts and coregistered. Resultant rCBF changes were evaluated parametrically through the formation of an image whose voxel values were based on the paired t statistic.

Amphetamine increased rCBF in two mesial prefrontal zones (Brodmann's areas 8 and 10), inferior orbital frontal lobe (area 11), brain stem (ventral tegmentum), anteromesial temporal lobe (amygdala), and anterior thalamus. Amphetamine decreased rCBF to motor cortex, visual cortex, fusiform gyrus, posterolateral temporal lobe, and right lateral temporal lobe.

Our data suggest that amphetamine induces focal increases and decreases in rCBF in healthy volunteers in areas primarily innervated by dopamine pathways and in areas with secondary (primarily limbic) affiliations. These data are consistent with glucose metabolic data from autoradiographic studies in animals, in which the largest increases are seen in brain stem, followed by striatum, thalamus, and frontal and sensory cortices. Frontopolar and temporal increases observed in our study appear to be unique to humans.