Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor, Mavoglurant

Principal Investigator: Dr. Ismene Petrakis. CTNA will test the central hypothesis that the heritable risk for alcoholism reflects dysfunction of cortico-striatal-midbrain circuitry, mediated by the interplay of glutamate and dopamine, that biases people to respond to drug-like rewards relative to delayed reward/punishments. This bias to respond to drug-like rewards leads to enhanced learning of alcohol-related associations, and facilitation of the development of habitual alcohol consumption. This project will test this hypothesis by assessing alcohol induced dopamine (DA) release in the striatum in at risk subjects and in patients with alcoholism to demonstrate that risk is associated with an increased alcohol-induced DA release in the striatum while the transition from risk to habit is associated with a decreased response.

This study builds on our current findings and extends the study of dopaminergic transmission to a high-risk population. It will characterize the biology of vulnerability versus habit. This could lead to developing a biomarker for identifying at risk subjects and possibly designing specific therapeutic strategies for prevention.