title: Intravenous ethanol increases dopamine release in the ventral striatum in humans: PET study using bolus-plus-infusion administration of [(11)C]raclopride.
abstract: Ethanol increases the interstitial dopamine (DA) concentration in the nucleus accumbens (NAcc) of experimental animals, but positron emission tomography (PET) studies using the single-bolus protocol of the [(11)C]-raclopride competition paradigm have yielded conflicting results in humans. To resolve disparate previous findings, we utilized the bolus-plus-infusion (B/I) method, allowing both baseline and intervention quantification of [(11)C]raclopride binding during a single 105-minute PET scan, to investigate possible ethanol-induced DA release in nine healthy male subjects. A 25-minute intravenous ethanol (7.6%) infusion, resulting in a 1.3 g/L mean blood ethanol concentration, was administered using masked timing during the PET scan. Automated region-of-interest analysis testing the difference between baseline (40-50 minutes) and intervention (60-85 minutes) revealed an average 12.6% decrease in [(11)C]raclopride binding in the ventral striatum (VST, P=0.003) including the NAcc. In addition, a shorter time interval from the start of ethanol infusion to the first subjective effect was associated with a greater binding potential decrease bilaterally in the VST (r=0.92, P=0.004), and the feeling of pleasure was associated with a decrease in binding potential values in both the caudate nucleus (r=-0.87, P=0.003) and putamen (r=-0.74; P=0.02). These results confirm that ethanol induces rapid DA release in the limbic striatum, which can be reliably estimated using the B/I method in one imaging session.
authors.affiliation: 1] Turku PET Centre, University of Turku, Turku, Finland [2] Department of Psychology, Åbo Akademi University, Åbo, Finland.
authors.forename: Sargo
authors.initials: S
authors.lastname: Aalto
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Ingman
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Kati
authors.initials: K
authors.lastname: Alakurtti
authors.affiliation: Division of Clinical Neurosciences, University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Valtteri
authors.initials: V
authors.lastname: Kaasinen
authors.affiliation: Department of Clinical Neurophysiology, Medical Imaging Centre, Pirkanmaa Hospital District, Tampere, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Virkkala
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.affiliation: Turku PET Centre, University of Turku, Turku, Finland.
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.affiliation: 1] Turku PET Centre, University of Turku, Turku, Finland [2] Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Harry
authors.initials: H
authors.lastname: Scheinin
mesh_terms: D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007262:Infusions, Intravenous; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride / Q000008:administration & dosage; D011868:Radioisotopes / Q000008:administration & dosage; D066328:Ventral Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; D011868:Radioisotopes; D000431:Ethanol; D020891:Raclopride; D004298:Dopamine