Mu-receptor agonism with alfentanil increases striatal dopamine D2 receptor binding in man.
Animal studies indicate that mu-opioids indirectly modulate neurotransmission in the nigrostriatal dopaminergic pathway. We used positron emission tomography (PET) to study the effects of alfentanil (a mu-opioid receptor agonist) on striatal dopamine D2 receptor binding in eight healthy male volunteers. D2 receptor binding was determined by using [(11)C]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 [(11)C]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 CO(2) (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.
Hagelberg
Nora
N
Department of Anesthesiology and Intensive Care, Turku University Central Hospital, Turku, Finland.
Kajander
Jaana K
JK
Någren
Kjell
K
Hinkka
Susanna
S
Hietala
Jarmo
J
Scheinin
Harry
H
D000328:Adult; D015760:Alfentanil / Q000009:adverse effects / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012016:Reference Values; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D015760:Alfentanil; D020891:Raclopride