Dopamine, Corticostriatal Connectivity, and Intertemporal Choice
“Value-based decisions optimize behavioral outcomes. Because delayed rewards are discounted, an increased tendency to choose smaller, immediate rewards can lead to suboptimal choice. Steep discounting of delayed rewards (impulsivity) characterizes subjects with frontal lobe damage and behavioral disorders including substance abuse. Correspondingly, animal studies and indirect evidence in humans suggest that lower dopamine in the frontal cortex contributes to steeper discounting by impairing corticostriatal function. To test this hypothesis directly, we performed a randomized, double-blind, counterbalanced, placebo-controlled study in which we administered the brain penetrant catechol-O-methyltransferase inhibitor tolcapone or placebo to healthy subjects performing a delay discounting task. Tolcapone significantly increased choice of delayed monetary rewards, and this tolcapone-induced increase covaried with increased BOLD activity in the left ventral putamen and anterior insula. Tolcapone also changed corticostriatal connectivity: specifically, by inducing a decrease in the coherence between ventral putamen and pregenual cingulate cortex. These results indicate that raising cortical dopamine levels attenuates impulsive choice by changing corticostriatal function.
The Journal of Neuroscience, 4 July 2012, 32(27): 9402-9409
Dr. Reinhardt’s interpretation: Impulsivity is a part of addictions of all kinds, including food addictions. Tolcapone inhibits the breakdown of dopamine, thus boosting available dopamine levels. It has significant hepatotoxicity and its use has been largely supplanted by Entacapone, which is much safer. Before rushing to generalize (or prescribe) it is worth noting that studies generally show that the boosting of dopamine may be inappropriate In obsessive compulsive disorder (OCD); transmission of dopamine from the substantia nigra to the basal ganglia and caudate nucleus-putamen (neostriatum) is thought to be increased in this disorder.