Increased Metabotropic Glutamate 2/3 Receptor Binding in the Perigenual Anterior Cingulate Cortex of Cloninger Type 2 Alcoholics: A Whole-Hemisphere Autoradiography Study

摘要

Aims: Metabotropic glutamate receptors 2 and 3 (mGluR2/3) contribute to control the level of glutamate in the synapse. In rodents, mGluR2/3 agonists attenuate the reinstatement of alcohol-seeking behavior. Linking possible alterations of the mGluR2/3 system to the etiology and type of alcoholism could provide valuable information for the development of novel mGluR2/3 function modulating therapies in addiction treatment. To date, mGluR2/3 binding density has not been studied in human alcoholics. We aimed to investigate the possible differences in mGluR2/3 binding between Cloninger type 1 anxiety-prone and type 2 impulsive alcoholics and controls. Methods: We performed a post-mortem whole-hemisphere autoradiography to study the mGluR2/3 binding density of 9 type 1 alcoholics, 8 type 2 alcoholics and 10 controls. [H-3]LY341495, a potent group II metabotropic glutamate receptor antagonist, was used as the radio-ligand with l-glutamate as a displacer. Results: [H-3]LY341495 binding density was statistically significantly increased (P = 0.046) in the perigenual anterior cingulate cortex (pACC) of type 2 alcoholics when compared with controls. In other brain areas, no significant difference between the groups was found. Conclusion: This preliminary study suggests that impulsive type 2 alcoholics might have alterations in the mGluR2/3 function in the pACC, a brain area presumed to be involved in the control of drug-seeking behaviors and self-control.