Effects of α-2A adrenergic receptor agonist on time and risk preference in primates

Subjective values of actions are influenced by the uncertainty and immediacy of expected rewards. Multiple brain areas, including the prefrontal cortex and basal ganglia, are implicated in selecting actions according to their subjective values. Alterations in these neural circuits, therefore, might contribute to symptoms of impulsive choice behaviors in disorders such as substance abuse and attention-deficit hyperactivity disorder (ADHD). In particular, the alpha-2A noradrenergic system is known to have a key influence on prefrontal cortical circuits, and medications that stimulate this receptor are currently in use for the treatment of ADHD. We tested whether the preference of rhesus monkeys for delayed and uncertain reward is influenced by the alpha-2A adrenergic receptor agonist, guanfacine. In each trial, the animal chose between a small, certain and immediate reward and another larger, more delayed reward. In half of the trials, the larger reward was certain, whereas in the remaining trials, the larger reward was uncertain. Guanfacine increased the tendency for the animal to choose the larger and more delayed reward only when it was certain. By applying an econometric model to the animal's choice behavior, we found that guanfacine selectively reduced the animal's time preference, increasing their choice of delayed, larger rewards, without significantly affecting their risk preference. In combination with previous findings that guanfacine improves the efficiency of working memory and other prefrontal functions, these results suggest that impulsive choice behaviors may also be ameliorated by strengthening prefrontal functions.