Decreased [3H]naloxone Binding in the Dentate Gyrus of Cloninger Type 1 Anxiety-Prone Alcoholics: A Postmortem Whole-Hemisphere Autoradiography Study.

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.