Simultaneous blockade of dopamine and noradrenaline reuptake promotes disadvantageous decision making in a rat gambling task

Abstract

The inability to make profitable long-term decisions has been implicated in several psychiatric disorders. There is emerging evidence to support a role for dopamine (DA) in decision making, but our understanding of the role of noradrenaline (NA) and serotonin (5-HT) in decision making, and of possible interactions between the three monoamines, is limited. Moreover, impulsivity has been associated with aberrant decision making, but the underlying mechanisms are incompletely understood. The purpose of this study is to improve our understanding of the neuropharmacological mechanisms of decision making and impulse control. We investigated the effects of amphetamine (0.25-1.0mg/kg) and selective reuptake inhibitors of DA (GBR12909; 2.5-10mg/kg), NA (atomoxetine; 0.3-3.0mg/kg), and 5-HT (citalopram; 0.3-3.0mg/kg) in a rat gambling task (rGT). Since the rGT allows for detection of impulsive action, i.e., premature responding, we also assessed the relationship between decision making and impulsivity. In the rGT, rats developed an optimal choice strategy from the first session onwards. Elevation of endogenous DA or NA levels increased and decreased impulsivity, respectively, but did not alter decision making. However, simultaneous blockade of DA and NA disrupted decision making, reflected by a relative decrease in choice for the advantageous choice options. Increasing 5-HT neurotransmission did not affect decision making or impulsivity. These data suggest important but complementary or redundant roles of DA and NA neurotransmission in decision-making processes based on reward probability and punishment. Moreover, impulse control and decision making in the rGT rely on dissociable mechanisms.