title: Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2/D3dopamine system.
abstract: Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2/D3receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2/D3dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2/D3receptor ligand [18F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2/D3binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BPND) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BPNDwas observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BPNDin extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D2/D3dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D2/D3receptors may hint at an addiction relevant trait.
authors.affiliation: Hospital of Psychiatry Muensingen and University Hospital of Psychiatry Bern, University of Bern, Bern 60, Switzerland.|Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pfeifer
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tüscher
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Hans Georg
authors.initials: HG
authors.lastname: Buchholz
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University and JARA-Translational Brain Medicine Aachen, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University and JARA-Translational Brain Medicine Aachen, Aachen, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University and JARA-Translational Brain Medicine Aachen, Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulzen
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Zimmermann
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Maus
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lieb
authors.affiliation: Institute for Human Genetics, RWTH Aachen University Medical Center, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eggermann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.|Department of Psychiatry, Psychotherapy and Psychosomatics, Agaplesion Markus Hospital, Frankfurt/Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Fehr
authors.affiliation: Department of Nuclear Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Schreckenberger
mesh_terms: D000328:Adult; D001549:Benzamides; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D000431:Ethanol / Q000494:pharmacology*; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics; D055815:Young Adult
chemical_list: D001549:Benzamides; D002492:Central Nervous System Depressants; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D065127:Dopamine D2 Receptor Antagonists; C485764:OPRM1 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017450:Receptors, Opioid, mu; D000431:Ethanol; C574003:fallypride
keywords: PET; alcohol; dopamine