Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Self-regulation failures in problem and pathological gambling (PPG) are linked to impaired prefrontal cortex control over subcortical structures.
• These impairments may affect reward evaluation in dopaminergic systems, contributing to addictive behaviors.

Purpose of the Study:

• To investigate if increasing cortical dopamine tone with tolcapone can reduce impulsivity (delay discounting) in PPG subjects.
• To determine if this effect is related to enhanced top-down control.

Main Methods:

• A randomized, double-blind, placebo-controlled, within-subject study involving 17 PPG subjects.
• Administration of the COMT inhibitor tolcapone or placebo.
• Performance of a delay discounting task during functional MRI (fMRI) scanning.

Main Results:

• Greater right inferior frontal cortex (RIFC) activity during placebo predicted greater impulsivity reduction with tolcapone.
• Tolcapone increased connectivity between RIFC and the right striatum, not RIFC activity itself.
• These changes correlated with reduced delay discounting.

Conclusions:

• Tolcapone enhances top-down control in PPG subjects, potentially by modulating RIFC-striatal connectivity.
• This mechanism may underlie the observed reduction in impulsivity.
• Findings suggest tolcapone as a potential treatment for gambling disorders and behavioral addictions.