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Opiate-Induced Dopamine Release Is Modulated by Severity of Alcohol Dependence: An [18F]Fallypride Positron Emission Tomography Study

  • Katja N. Spreckelmeyer
    Correspondence
    Address correspondence to Katja N. Spreckelmeyer, Ph.D., Department of Psychiatry, Rheinisch-Westfälische Technische Hochschule Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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  • Michael Paulzen
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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  • Mardjan Raptis
    Affiliations
    Department of Nuclear Medicine, RWTH Aachen University, Aachen, Germany
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  • Thomas Baltus
    Affiliations
    Department of Anaesthesiology, RWTH Aachen University, Aachen, Germany
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  • Sabrina Schaffrath
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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  • Julia Van Waesberghe
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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  • Magdalena M. Zalewski
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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  • Frank Rösch
    Affiliations
    Institute of Nuclear Chemistry, Johannes-Gutenberg-University Mainz, Mainz, Germany
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  • Ingo Vernaleken
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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  • Wolfgang M. Schäfer
    Affiliations
    Department of Nuclear Medicine, St. Franziskus Hospital, Mönchengladbach, Germany
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  • Gerhard Gründer
    Affiliations
    Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, and Jülich-Aachen Research Alliance (JARA)—Translational Brain Medicine, Aachen, Germany
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      Background

      Preclinical data implicate the reinforcing effects of alcohol to be mediated by interaction between the opioid and dopamine systems of the brain. Specifically, alcohol-induced release of β-endorphins stimulates μ-opioid receptors (MORs), which is believed to cause dopamine release in the brain reward system. Individual differences in opioid or dopamine neurotransmission have been suggested to be responsible for enhanced liability to abuse alcohol. In the present study, a single dose of the MOR agonist remifentanil was administered in detoxified alcohol-dependent patients and healthy control subjects to mimic the β-endorphin-releasing properties of ethanol and to assess the effects of direct MOR stimulation on dopamine release in the mesolimbic reward system.

      Methods

      Availability of D2/3 receptors was assessed before and after single-dose administration of the MOR agonist remifentanil in 11 detoxified alcohol-dependent patients and 11 healthy control subjects with positron emission tomography with the radiotracer [18F]fallypride. Severity of dependence as assessed with the Alcohol Use Disorders Identification Test was compared with remifentanil-induced percentage change in [18F]fallypride binding (Δ%BPND).

      Results

      The [18F]fallypride binding potentials (BPNDs) were significantly reduced in the ventral striatum, dorsal putamen, and amygdala after remifentanil application in both patients and control subjects. In the patient group, ventral striatum Δ%BPND was correlated with the Alcohol Use Disorders Identification Test score.

      Conclusions

      The data provide evidence for a MOR-mediated interaction between the opioid and the dopamine system, supporting the assumption that one way by which alcohol unfolds its rewarding effects is via a MOR-(γ-aminobutyric acid)-dopamine pathway. No difference in dopamine release was found between patients and control subjects, but evidence for a patient-specific association between sensitivity to MOR stimulation and severity of alcohol dependence was found.

      Key Words

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