Researchers have discovered that elevating the level of the neurotransmitter dopamine in the frontal lobe of the brain can significantly decrease impulsivity in healthy adults.
The finding is important as impulsiveness is a risk factor for substance abuse.
“Impulsivity is a risk factor for addiction to many substances, and it has been suggested that people with lower dopamine levels in the frontal cortex tend to be more impulsive,” said lead author Andrew Kayser, Ph.D.
Researchers from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco performed a double-blinded placebo study. The study has been published in the Journal of Neuroscience.
In the research, 23 adult research participants were given either tolcapone, a medication approved by the Food and Drug Administration (FDA) that inhibits a dopamine-degrading enzyme, or a placebo.
Investigators then gave the participants a task that measured impulsivity, asking them to make a hypothetical choice between receiving a smaller amount of money immediately (“smaller sooner”) or a larger amount at a later time (“larger later”).
Each participant was tested twice, once with tolcapone and once with placebo.
More impulse (at baseline) participants were more likely to choose the less impulsive “larger later” option after taking tolcapone than they were after taking the placebo.
Magnetic resonance imaging conducted while the participants were taking the test confirmed that regions of the frontal cortex associated with decision-making were more active in the presence of tolcapone than in the presence of placebo.
“To our knowledge, this is the first study to use tolcapone to look for an effect on impulsivity,” said Kayser.
The study is a proof-in-concept investigation and was not designed to investigate the reasons that reduced dopamine is linked with impulsivity.
However, explained Kayser, scientists believe that impulsivity is associated with an imbalance in dopamine between the frontal cortex, which governs executive functions such as cognitive control and self-regulation, and the striatum, which is thought to be involved in the planning and modification of more habitual behaviors.
“Most, if not all, drugs of abuse, such as cocaine and amphetamine, directly or indirectly involve the dopamine system,” said Kayser.
“They tend to increase dopamine in the striatum, which in turn may reward impulsive behavior. In a very simplistic fashion, the striatum is saying ‘go,’ and the frontal cortex is saying ‘stop.’ If you take cocaine, you’re increasing the ‘go’ signal, and the ‘stop’ signal is not adequate to counteract it.”
Kayser and his research team plan a follow-up study of the effects of tolcapone on drinking behavior.
“Once we determine whether drinkers can safely tolerate this medication, we will see if it has any effect on how much they drink while they’re taking it,” said Kayser.
Currently, Tolcapone is approved as a medication for Parkinson’s disease — a disease in which a chronic deficit of dopamine inhibits movement.