SPECT imaging of striatal dopamine release after amphetamine challenge

This study assesses the feasibility of using SPECT to image intrasynaptic dopamine release in human striatum following dextroamphetamine sulfate (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 underwent 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 availability, measured as the specific-to-nonspecific equilibrium partition coefficient (V₃''). The d-amphetamine injection induced marked increase 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 anxiety response was milder and not correlated with the decrease in 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.