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 [(11)C]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-controlled 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 [(11)C]FLB 457 in the medial frontal cortex (P=0.0027), 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 [(11)C]FLB 457 BP in the anterior cingulate cortex (P<0.001). Alfentanil induced euphoria (P=0.003) and analgesia (P=0.006) Cheerfulness (r=0.918, P=0.001) and euphoria (r=0.982, P<0.001) were associated with increased BP of [(11)C]FLB 457 in the left posterior cingulate cortex, but the analgesic effect of alfentanil did not correlate with changes in [(11)C]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.
Hagelberg
Nora
N
Turku PET Centre, University of Turku, P.O. Box 52, FIN 20521 Turku, Finland. nora.hagelberg@tyks.fi
Aalto
Sargo
S
Kajander
Jaana
J
Oikonen
Vesa
V
Hinkka
Susanna
S
Någren
Kjell
K
Hietala
Jarmo
J
Scheinin
Harry
H
D000328:Adult; D015760:Alfentanil / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012457:Salicylamides / Q000493:pharmacokinetics; D013788:Thalamus / Q000033:anatomy & histology / Q000187:drug effects; D014055:Tomography, Emission-Computed / Q000379:methods
D002247:Carbon Isotopes; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D009294:Narcotics; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C065065:FLB 457; D015760:Alfentanil