Increased [³H]quisqualic acid binding density in the dorsal striatum and anterior insula of alcoholics: A post-mortem whole-hemisphere autoradiography study

Abstract

The function of group I metabotropic glutamate receptors mGluR1 and mGluR5 is involved in the hyperglutamatergic state caused by chronic alcohol. Preclinical studies suggest that group I mGluR modulation could serve as a novel treatment of alcoholism. Considering the wide role of glutamatergic neurochemistry in addiction, group I mGluR binding was studied in brain areas involved in decision-making, learning and memory.Post-mortem whole hemisphere autoradiography was used to study the binding density of [³H]quisqualic acid, a potent group I mGluR agonist, in 9 Cloninger type 1 alcoholics, 8 Cloninger type 2 alcoholics and 10 controls. Binding was studied in the dorsal striatum, hippocampus and cortex.Alcoholics displayed a trend towards increased [³H]quisqualic acid binding in all brain areas. The most robust findings were in the putamen (p = 0.006) and anterior insula (p = 0.005), where both alcoholic subtypes displayed increased binding compared to the controls.These findings suggest altered group I mGluR function in alcoholic subjects in the dorsal striatum, which is involved in habitual learning, and in the anterior insula, which has a pivotal role in the perception of bodily sensations. Increased [³H]quisqualic acid binding might suggest a beneficial impact of mGluR1/5 modulators in the treatment of alcoholism.