Research Component 2: Prisciandaro & Mellick

Effects of a Novel mGluR5 Negative Allosteric Modulator on Alcohol Drinking, Neurochemistry, and Brain Reactivity to Alcohol Cues in Alcohol Use Disorder

Principal Investigator: James Prisciandaro, Ph.D.
Co-Investigator: William Mellick, Ph.D.
Collaborator/Consultant: Robert Malcolm, M.D.

This research component focuses on evaluating the therapeutic potential of a novel medication (GET73) in treating individuals with AUD. Preclinical and clinical evidence suggests that GET73, a metabotropic glutamate subtype 5 receptor (mGluR5) negative allosteric modulator may reduce alcohol consumption. This project will enroll non-treatment-seeking individuals with AUD (referred by the ARC Clinical Intake & Assessment Core) to test whether GET73, compared to placebo, reduces drinking in a bar-lab paradigm and in the natural environment. Further, neuroimaging indicators will probe purported mechanisms of GET73 action. Specifically, MR Spectroscopy and fMRI will be used to examine whether GET73 mitigates AUD-related neurochemical adaptations (cortical glutamate/GABA balance) and alcohol cue-induced brain activation in cortical and striatal areas, respectively.

Specific Aims of the project include:

• Test the hypothesis that GET73, relative to placebo, will reduce both bar-lab and naturalistic alcohol drinking.
• Test the hypothesis that GET73, relative to placebo and to baseline, will increase fronto-cortical glutamate and GABA levels (1H-MRS), and these effects will mediate GET73 effects on drinking.
• Test the hypothesis that GET73, relative to placebo and to baseline, will reduce vmPFC, OFC, ACC, and VS activation to alcohol cues (fMRI), and these effects will mediate GET73 effects on drinking.