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A Study of Neural Circuit Responses to Catechol-O-methyl Transferase (COMT) Inhibitors

2014-08-27 03:12:22 | BioPortfolio

Summary

In this study, we seek to understand the effect of tolcapone, and FDA-approved COMT inhibitor that crosses the blood-brain barrier, on reward choice and response inhibition, two measures we have previously shown to be altered in subjects with alcoholism. We now plan to test the hypothesis that COMT regulation of cortical dopamine levels is critical for regulation financial choices. Specifically, we propose that the lower levels of cortical dopamine present in individuals with the val158val COMT genotype reduces the inhibitory effect of frontal cortical areas on impulsive choice; an idea that extends previous hypotheses about the negative consequences of decreased prefrontal dopamine levels on inhibitory control. Moreover, this hypothesis suggests that inhibiting COMT may slow the degradation of dopamine and thereby decrease impulsivity.

Description

Drug consumption despite adverse consequences is a defining feature of human addiction (DSM-IV-TR, 2004). Impulsivity, a tendency to choose an immediate action despite delayed adverse consequences, is a major risk factor for tobacco, psychostimulant, opioid and alcohol abuse. In humans, impulsivity can be quantified by presenting subjects with a choice between a small immediate monetary reward or a larger but delayed reward. We recently found that the val158val allele for the enzyme catechol-O-methyltransferase (COMT), which is associated with more rapid cortical dopamine catabolism and thus lower cortical dopamine levels correlates with greater impulsivity and greater fMRI blood oxygen level dependent (BOLD) signal in dorsolateral prefrontal and posterior parietal cortices.

The first phase of the study will involve healthy controls. The second phase of the study will involve abstinent alcoholics matched for age, education, and gender. Subjects will range in age between 18 and 50 years old.

Study Design

Allocation: Randomized, Control: Placebo Control, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Conditions

Impulsive Behavior

Intervention

Tolcapone, Placebo

Location

University of California, Berkeley
Berkeley
California
United States
94704

Status

Recruiting

Source

University of California, San Francisco

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:22-0400

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Medical and Biotech [MESH] Definitions

An act performed without delay, reflection, voluntary direction or obvious control in response to a stimulus.

The tendency to devalue an outcome as a function of its temporal delay or probability of achievement. It can be evaluated in a psychological paradigm that involves the choice between receiving a smaller immediate reward or a larger delayed reward, and may be used to provide a measure of impulsive behavior.

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc.

Animal behavior associated with the nest; includes construction, effects of size and material; behavior of the adult during the nesting period and the effect of the nest on the behavior of the young.

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