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Departments of Psychiatry, Anesthesiology and Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
Department of Veterans Affairs Medical Center, West Haven, Connecticut
Division of Nuclear Medicine, Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania
Correspondence: For correspondence or reprints contact: Marc Laruelle, MD, Department of Psychiatry, Yale School of Medicine, West Haven VA Medical Center/116A2, West Haven, CT 06516.
ABSTRACT
This study assesses the feasibility of using SPECT to image intrasynaptic dopamine release in human striatum following dextroamphetamine sultate (d-amphetamine) challenge testing. Methods: A bolus plus constant infusion administration schedule of the D2 receptor radiotracer [123I]iodobenzamide ([123I]IBZM) was used to obtain a stable baseline for reliable quantitation of the d-amphetamine effect. Eight healthy subjects first under went a controlled experiment to demonstrate that stable levels of striatal and occipital activities could be maintained from 150 to 420 min during programmed infusion of the tracer. Next, seven subjects underwent the experiment with d-amphetamine. The experimental conditions were identical except that 0.3 mg/kg amphetamine was injected intravenously at 240 min. The behavioral effects of d-amphetamine were measured by self-rating on the following analog scales: euphoria, alertness, restlessness and anxiety. Results: The d-amphetamine injection induced a 15%± 4% (mean ± s.d.) decrease in D2 receptor availabllfty, measured as the specific-to-nonspecific equilibrium partition coefficient (V3"). Thed-amphetamine injection induced markedi ncrease in euphoria, alertness and restlessness scores. The intensity of these behavioral responses correlated with the decrease in D2 availability measured with SPECT. In contrast, the anxioty response was milder and not correlated with the decreasein D2 availability. Conclusion: These studies demonstrate the feasibility of using [123I]IBZM programmed infusion and SPECT imaging to measure endogenous dopamine release after d-amphetamine challenge and to study brain neurochemical correlates of emotions.
Key Words: single-photon emission computed tomography • dopamine D2 receptors • iodine-123-IBZM • equilibrium analysis
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