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Journal of Neuroscience, Vol 11, 1907-1917, Copyright © 1991 by Society for Neuroscience
The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia
DG Daniel, DR Weinberger, DW Jones, JR Zigun, R Coppola, S Handel, LB Bigelow, TE Goldberg, KF Berman and JE Kleinman
Clinical Brain Disorders Branch, Saint Elizabeths, National Institute of of Mental Health, Washington, D.C. 20032.
To explore the role of monoamines on cerebral function during specific
prefrontal cognitive activation, we conducted a double-blind placebo-
controlled crossover study of the effects of 0.25 mg/kg oral
dextroamphetamine on regional cerebral blood flow (rCBF) as determined by
133Xe dynamic single-photon emission-computed tomography (SPECT) during
performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor
control task. Ten patients with chronic schizophrenia who had been
stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated.
Amphetamine produced a modest, nonsignificant, task- independent, global
reduction in rCBF. However, the effect of amphetamine on task-dependent
activation of rCBF (i.e., WCST minus control task) was striking. Whereas on
placebo no significant activation of rCBF was seen during the WCST compared
with the control task, on amphetamine significant activation of the left
dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean
number of correct responses and the mean conceptual level increased (p less
than 0.05) with amphetamine relative to placebo. In addition, with
amphetamine, but not with placebo, a significant correlation (p = - 0.71; p
less than 0.05) emerged between activation of DLPFC rCBF and performance of
the WCST task. These findings are consistent with animal models in which
mesocortical catecholaminergic activity modulates and enhances the
signal-to-noise ratio of evoked cortical activity.
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