Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor, Mavoglurant
Overview
Principal Investigator: Dr. Godfrey Pearlson. CTNA will use the mGluR5 negative allosteric modulator drug mavoglurant as a probe in conjunction with 4 functional MRI paradigms to understand how the drug targets the brain systems implicated in familial alcoholism risk. These fMRI paradigms are 1. Response to rewards and punishments (monetary incentive delay task, MID), 2. Inhibiting response to prepotent cues (go/no-go task, GNG), 3. Responsiveness to alcohol-related as opposed to soft-drink or neutral cues (alcohol cue reactivity task, ACR) and 4. the ability to benefit from “model-based,” goal-directed learning strategies versus “model-free” learning, that is a less advantageous strategy involving dominance of immediate rewards or habit over behavior (multi-stage decision-making, MSDM task). This project will compare equal numbers of individuals who have strong positive family history of alcoholism and are thus at increased risk for the disorder (family history positive or FHP) to those who have no affected relatives (family history negative or FHN).
Activities
Participation Opportunities
Relevant Publications
- Urban NB, Kegeles LS, Slifstein M, Xu X, Martinez D, Sakr E, Castillo F, Moadel T, O'Malley SS, Krystal JH, Abi-Dargham A. (2010). Sex differences in striatal dopamine release in young adults after oral alcohol challenge: a positron emission tomography imaging study with [¹¹C]raclopride. Biol Psychiatry. 68(8):689-96. PMID: 20678752.
- Martinez D, Slifstein M, Gil R, Hwang DR, Huang Y, Perez A, Frankle WG, Laruelle M, Krystal J, Abi-Dargham A. (2009). Positron emission tomography imaging of the serotonin transporter and 5-HT(1A) receptor in alcohol dependence. Biol Psychiatry. 65(2):175-80. PMID: 18962444.
- Martinez D, Gil R, Slifstein M, Hwang DR, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J, Laruelle M, Abi-Dargham A. (2005). Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry. 58(10):779-86. PMID: 16018986.
- Urban NB, Slifstein M, Meda, S, Xu X, Ayoub R, Medina O, Pearlson GD, Krystal JH, Abi-Dargham A. (In Review). Imaging reward function with PET and fMRI. Psychopharmacology.