Summary: A new study reveals that Tolcapone, a drug that improves dopamine, strengthens the brain circuits involved in self -control while reducing alcohol intake in people with alcohol consumption disorder (Aud). The drug increases the activity in the lower frontal turn, part of the prefrontal cortex, which supports the inhibitory control.
The participants who were given the Tolcapona showed improved behavioral performance in a task of inhibition of the response and a decrease in alcohol consumption behavior. These findings suggest that directing dopamine in the prefrontal cortex could open a new route to develop more effective treatments for Aud.
Key facts
New objective: unlike current treatments, Tolcapona addresses deteriorated self -control instead of just cravings or extraction.
Source: Elsevier
Researchers have identified a new promising strategy to treat alcohol consumption (Aud) disorder.
A new study found that the drug that increases Tolcapone dopamine increases the activity in the prefrontal cortex (PFC) during self -control tasks. A greater activation of the lower frontal circumvolution, part of the PFC, was associated with better behavioral control and reduced alcohol consumption.
The findings of this new study in biological psychiatry: cognitive neuroscience and neuroimagen indicate that medications with a similar mechanism could be used one day to treat AUD.
Aud is a devastating disorder characterized by the loss of control over alcohol consumption, for which existing pharmacological treatments are modestly effective. Most of the pharmacological treatments approved and out of label for the Objective Alcohol Antojo and/or the symptoms of alcohol withdrawal.
“We desperately need new pharmacological treatments for Aud. Our study changes the approach of ‘rescue’ the inhibitory control of deterioration, which is the ability of the brain to stop the thoughts or unwanted actions, a function often committed to Aud,” says principal author Joseph P. Schacht, PHD, department of Psychiatry, University of the Colorado Medicine School.
“Our study suggests that medications that increase prefrontal dopamine are an important advance to follow.”
The study involved 64 participants with AUs that were assigned randomly to receive Tolcapone, a medication approved by the FDA that increases dopamine in the PFC by suppressing the catechol-O-methyltransferase (COMT), an enzyme that degrades the dopmine or a placebo for eight days.
The participants completed a behavior control task called “stop signal” while submitting functional neuroimaging (FMRI), during which they had to try to avoid pressing a button on certain tests.
This task reliably causes the activation of PFC regions that underlie the response inhibition. The analysis showed that Tolcapona increased the activation of the cortical areas involved in inhibitory control, as evaluated by the FMRI blood oxygenation response.
The main author Drew E. Winters, PHD, Department of Psychiatry, Faculty of Medicine of the University of Colorado, points out: “Based on previous studies, we anticipate that a higher lower frontal turn activation would be associated with better behavioral control, but we were pleasantly surprised to discover that it was also associated with reduced alcohol consumption.
“This association validates the importance of deteriorated control in Aud Pathophysiology.”
Editor in Chief of Biological Psychiatry: Cognitive Neuroscience and Neuroimagen Cameron S. Carter, MD, Irvine Medicine Faculty of the University of California, concludes: “Dopamine is a crucial neurotransmitter involved in pleasure, motivation, reward and control and decision making.
“The findings of this study underline the importance of addressing specific brain circuits that govern self -control to reduce problematic consumption.
“Future research should continue to investigate the neurobiological mechanisms of Tolcapona and other cortical dopamine modulators to develop more effective treatments for Aud.”
About this neuroscience and the research news of alcohol consumption disorder
Author: Eileen Leahy
Source: Elsevier
Contact: Eileen Leahy – Elsevier
Image: The image is accredited to Neuroscience News
Original research: open access.
“Effects of the suppression of COMT on a randomized trial in the neural correlates of inhibitory processing between people with alcohol consumption disorder” by Joseph P. Schacht et al. Biological psychiatry: cognitive neuroscience and neuroimagen
Abstract
Effects of the suppression of COMT in a randomized trial in the neural correlates of inhibitory processing among people with alcohol consumption disorder
Background
The deregulation of inhibitory control is a central characteristic of alcohol consumption (Aud) disorder, and is mediated, in part, by the regulation of catechol-o-methyltransferase (COMT) of the cortical dopaminergic neurotransmission. The Tolcapone, a COMT inhibitor of the brain penetrating, enhances the release of evoked dopamine and can improve inhibitory control in Aud.
Methods
Participants who do not seek to treatment with AUD (n = 64) were randomized to Tolcapone (titled 200 mg Tid) or placebo for 8 days and completed a FMRI stop signal task on the 1st day of study (before the ingestion of medications) and 7. The brain areas in which the activation for the contrast of the successful vs. Non -successful detention tests (SS> SS) among medication groups between medication groups between the 7th were identified on day 7.
The activation of these areas, and their functional connectivity with other areas, was tested for association with changes in the drink during the medication period and with the reaction time of the stop signal, an inhibitory control behavior index.
Results
The Tolcapona group demonstrated a greater activation of SS> is in the right dorsolateral prefrontal cortex and lower frontal turn (IFG). In the Tolcapona group, a greater activation of both areas was associated with better inhibitory control, and a greater activation of IFG was associated with reduced alcohol consumption. The increase in connectivity between IFG and the right previous insula was associated with a drink reduction, and between IFG and anterior cingulated cortex with improved inhibitory control.
Conclusions
Tolcapona increased the activation of the cortical areas involved in inhibitory control. The associations between the increase in IFG activation and connectivity, improved inhibitory control and reduced consumption suggest that pharmacological interventions that increase cortical dopamine can rescue deregulated inhibitory control between people with Aud.
