Alfentanil increases cortical dopamine D2/D3 receptor binding in healthy subjects

Animal studies have shown that opioids modulate the function of dopaminergic neurons. The effect of alfentanil on cortical and thalamic binding of the D2/D3 receptor ligand [C-11]FLB 457 was evaluated in eight healthy subjects with positron emission tomography. The simplified reference tissue model was used to calculate tracer binding potential (BP) during a baseline condition and target-con trot led infusion of alfentanil, and the results were analyzed using a comparison group not receiving opioid. Behavioral and analgesic effects of alfentanil were also evaluated. In the region-of-interest analysis. alfentanil increased the BP of [C-11]FLB 457 in the medial frontal cortex (P = 0.028), dorsolateral prefrontal cortex (P = 0.027), Superior temporal cortex (P = 0.028), and medial thalamus (P = 0.003). These results were confirmed in a voxel-based analysis, which further revealed an opioid-induced increase in [C-11]FLB 457 BP in the anterior cingulate cortex (P < 0.001). Alfentanil induced euphoria (P = 0.03) and analgesia (P = 0.006). Cheerfulness (r = 0.982, P < 0.001) and euphoria (r = 0.918, P = 0.001) were associated with increased BP of [C-11]FLB 457 in the left posterior cingulate cortex. but the analgesic effect of alfentanil did not correlate with changes in [C-11]FLB 457 BP. The results of this study demonstrate opioid-dopamine interactions in frontal and temporal cortical regions and the thalamus in healthy subjects. Increased D2/D3 tracer binding during opioid infusion may reflect decreased synaptic dopamine levels. The association of the uplifting effect of alfentanil with increased D2/D3 binding in the posterior cingulate cortex suggests that cortical dopamine may be involved in the behavioral effects of opioids. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.