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

Overview

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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

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.

Participation Opportunities

Healthy control subjects with a biological father who drinks heavily

Contact: 203-932-5711 x 5688. All calls are confidential

We are looking for healthy individuals, ages 21-30, to take part in a research study designed to look at the function of dopamine receptors using PET imaging. This study will require an initial screening session which will take about 2 hours. If you are found to be eligible then you will be scheduled for an MRI which will take about 30 minutes and 2 PET Scans (on different days) which will take about 6 hours each. Both scans will be done after oral administration of a drink. On one of the scan days, the drink will contain alcohol. We may ask you to come for an additional day to complete neuropsychological assessments. You will be able to complete this study in 4-5 test days. Compensation is up to $765 for participation in all test days. HIC 1008007217, HSS IP0035

Read about other participation opportunities

Relevant Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.