μ‐Receptor agonism with alfentanil increases striatal dopamine D2 receptor binding in man

Abstract

Animal studies indicate that μ‐opioids indirectly modulate neurotransmission in the nigrostriatal dopaminergic pathway. We used positron emission tomography (PET) to study the effects of alfentanil (a μ‐opioid receptor agonist) on striatal dopamine D2 receptor binding in eight healthy male volunteers. D2 receptor binding was determined by using [¹¹C]raclopride as radioligand. Each subject underwent two PET sessions on the same day, the first without the drug (control) and the second during alfentanil infusion. Alfentanil was administered as target‐controlled infusion to maintain pseudo steady‐state plasma concentration of 80 ng/ml throughout the PET session. A freeze lesion model was used for pain testing at the end of both PET sessions. A mechanical pain stimulus of 5 N was rated by the subjects using a visual analog scale. Regions of interest for the putamen, caudate nucleus, and cerebellum were drawn on MRI images and transferred to PET images. Alfentanil increased the binding potential of [¹¹C]raclopride in the putamen by 6.0% (P = 0.04) and in the caudate nucleus by 7.4% (P = 0.008). Alfentanil caused a small reduction in respiratory rate (P = 0.046) and oxygen saturation (P < 0.001), and a moderate consistent increase in end‐tidal CO₂ (P < 0.001). Pain scores were significantly smaller after alfentanil PET scan (median VAS 9 (0–42) vs. 23.5 (15–52), P = 0.008). These results indicate that pharmacologically relevant concentrations of alfentanil increase D2 dopamine receptor binding in the striatum in man. This increase is assumed to reflect reduced dopamine release. Synapse 45:25–30, 2002.