Differential effects of D-amphetamine on red and blue light-induced photic activation: A novel BOLD fMRI assay of human dopamine function

The neurotransmitter dopamine (DA) is implicated in the pathophysiology of central nervous system (CNS) illnesses including Parkinson's disease, attention deficit disorder, schizophrenia, and substance abuse. A better understanding of CNS DA function would be of importance in improving our understanding of these conditions. Several lines of evidence suggest that exploring visual system function may be a useful paradigm for examining DA function. Clinical and basic science findings suggest that the visual response to blue light might prove a useful assay of CNS DA tone. To test this hypothesis, we used the functional magnetic resonance imaging (fMRI) BOLD method to measure visual cortical activation in human subjects (N = 6) in response to 8 Hz flashing red and blue light stimuli during placebo conditions and during the oral administration of 2.5 mg of D-amphetamine, a drug known to increase synaptic concentrations of DA and other monoamine neurotransmitters. There was no effect Of D-amphetamine administration on the percent BOLD signal change to red or blue light. However, there was a specific augmentation of the spatial extent of activation (as measured by the number of activated pixels; P = 0.018) to blue, but not red light following D-amphetamine administration. This finding is consistent with our hypothesis that blue light function may have utility as an assay of CNS DA tone. However, several limitations to the study, including the small sample size, low dosage of D-amphetamine, and the fact that D-amphetamine increases synaptic concentrations of DA and other monoamine neurotransmitters do not permit a conclusion regarding a specific role for DA in the observed increase in spatial activation to blue light in the amphetamine condition.