Virpi Laukkanen1,2, Olli Kärkkäinen3, Hannu Kautiainen4,5, Jari Tiihonen1,6, Markus Storvik3. 1. Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. 2. Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland. 3. Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio, Finland. 4. Unit of Primary Health Care, Helsinki University Central Hospital, Helsinki, Finland. 5. Department of General Practice, University of Helsinki, Helsinki, Finland. 6. Department of Clinical Neuroscience, Karolinska Institutet, Karolinska sjukhuset, Stockholm, Sweden.
Abstract
BACKGROUND: The opioid system of the central nervous system plays an essential role in the regulation of the rewarding effects of alcohol. Alcohol affects mu-opioid receptor (MOR) function. Enhanced MOR function inhibits the GABAergic inhibition of the nucleus accumbens (Nac), which leads to a release of dopamine in the Nac. Of the few pharmaceutical treatments for alcoholism, the MOR antagonists naltrexone and nalmefene benefit most a subset of alcoholics who are characterized with early onset and impulsivity. Our aim was to investigate possible differences in the binding density of [³H]naloxone, a MOR competitive antagonist, between Cloninger type 1 anxiety-prone and harm-avoidant alcoholics, Cloninger type 2 impulsive and antisocial alcoholics, and healthy controls in brain areas that are essential for reward, learning, impulse-control, and mood regulation. METHODS: We used postmortem whole-hemisphere autoradiography with [³H]naloxone, as a binding ligand. A subsequent autoradiography was performed with [³H]DAMGO, a selective MOR agonist. RESULTS: Cloninger type 1 alcoholics displayed decreased [³H]naloxone binding density in all studied brain areas. This trend reached statistical significance in the dentate gyrus, where type 1 alcoholics' [³H]naloxone binding density was significantly decreased (p = 0.019) when compared to controls. A similar trend of decreased binding in type 1 alcoholics was observed in the [³H]DAMGO study. CONCLUSIONS: Our finding suggest that Cloninger type 1 anxiety-prone alcoholics may have an altered [³H]naloxone binding in brain areas related to reward, impulse-control, mood, and learning. The finding lends support to the idea of Cloninger type 1 anxiety-prone alcoholics responding weaker to the opioidergic pharmaceuticals of the treatment of alcoholism than Cloninger type 2 impulsive alcoholics.
BACKGROUND: The opioid system of the central nervous system plays an essential role in the regulation of the rewarding effects of alcohol. Alcohol affects mu-opioid receptor (MOR) function. Enhanced MOR function inhibits the GABAergic inhibition of the nucleus accumbens (Nac), which leads to a release of dopamine in the Nac. Of the few pharmaceutical treatments for alcoholism, the MOR antagonists naltrexone and nalmefene benefit most a subset of alcoholics who are characterized with early onset and impulsivity. Our aim was to investigate possible differences in the binding density of [³H]naloxone, a MOR competitive antagonist, between Cloninger type 1 anxiety-prone and harm-avoidant alcoholics, Cloninger type 2 impulsive and antisocial alcoholics, and healthy controls in brain areas that are essential for reward, learning, impulse-control, and mood regulation. METHODS: We used postmortem whole-hemisphere autoradiography with [³H]naloxone, as a binding ligand. A subsequent autoradiography was performed with [³H]DAMGO, a selective MOR agonist. RESULTS: Cloninger type 1 alcoholics displayed decreased [³H]naloxone binding density in all studied brain areas. This trend reached statistical significance in the dentate gyrus, where type 1 alcoholics' [³H]naloxone binding density was significantly decreased (p = 0.019) when compared to controls. A similar trend of decreased binding in type 1 alcoholics was observed in the [³H]DAMGO study. CONCLUSIONS: Our finding suggest that Cloninger type 1 anxiety-prone alcoholics may have an altered [³H]naloxone binding in brain areas related to reward, impulse-control, mood, and learning. The finding lends support to the idea of Cloninger type 1 anxiety-prone alcoholics responding weaker to the opioidergic pharmaceuticals of the treatment of alcoholism than Cloninger type 2 impulsive alcoholics.
Authors: Derik Hermann; Natalie Hirth; Matthias Reimold; Anil Batra; Michael N Smolka; Sabine Hoffmann; Falk Kiefer; Hamid R Noori; Wolfgang H Sommer; Gerald Reischl; Christian la Fougère; Karl Mann; Rainer Spanagel; Anita C Hansson Journal: Neuropsychopharmacology Date: 2016-08-11 Impact factor: 7.853