SPECT IMAGING OF STRIATAL DOPAMINE RELEASE AFTER AMPHETAMINE CHALLENGE

This study assesses the feasibility of using SPECT to image intrasynap tic dopamine release in human striatum following dextroamphetamine sul fate (d-amphetamine) challenge testing. Methods: A bolus plus constant infusion administration schedule of the D2 receptor radiotracer [I-12 3]iodobenzamide ([I-123]IBZM) was used to obtain a stable baseline for reliable quantitation of the d-amphetamine effect. Eight healthy subj ects first underwent a controlled experiment to demonstrate that stabl e 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 injec ted 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 injec tion induced a 15% +/- 4% (mean +/- s.d.) decrease in D2 receptor avai lability, measured as the specific-to-nonspecific equilibrium partitio n coefficient (V-3 ''). The d-amphetamine injection induced marked inc rease in euphoria, alertness and restlessness scores. The intensity of these behavioral responses correlated with the decrease in D2 availab itity measured with SPECT. In contrast, the anxiety response was milde r and not correlated with the decrease in D2 availability. Conclusion: These studies demonstrate the feasibility of using [I-123]IBZM progra mmed infusion and SPECT imaging to measure endogenous dopamine release after d-amphetamine challenge and to study brain neurochemical correl ates of emotions.