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.
Department of Anesthesiology and Intensive Care, Turku University Central Hospital, Turku, Finland.
Nora
N
Hagelberg
Jaana K
JK
Kajander
Kjell
K
Någren
Susanna
S
Hinkka
Jarmo
J
Hietala
Harry
H
Scheinin
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