Dopaminergic Modulation of Risk-Based Decision Making

Psychopharmacological studies have implicated the mesolimbic dopamine (DA) system in the mediation of cost/benefit evaluations about delay or effort-related costs associated with larger rewards. However, the role of DA in risk-based decision making remains relatively unexplored. The present study investigated the effects of systemic manipulations of DA transmission on risky choice using a probabilistic discounting task. Over discrete trials, rats chose between two levers; a press on the 'small/certain' lever always delivered one reward pellet, whereas a press on the other, 'large/risky' lever delivered four pellets, but the probability of receiving reward decreased across the four trial blocks (100, 50, 25, 12.5%). In separate groups of well-trained rats we assessed the effects of the DA releaser amphetamine, as well as receptor selective agonists and antagonists. Amphetamine consistently increased preference for the large/risky lever; an effect that was blocked or attenuated by co-administration of either D-1 (SCH23390) or D-2 (eticlopride) receptor antagonists. Blockade of either of these receptors alone induced risk aversion. Conversely, stimulation of D-1 (SKF81297) or D-2 (bromocriptine) receptors also increased risky choice. In contrast, activation of D-3 receptors with PD128,907 reduced choice of the large/risky lever. Likewise, D-3 antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D-4 receptors did not reliably alter behavior. These findings indicate that DA has a critical role in mediating risk-based decision making, with increased activation of D-1 and D-2 receptors biasing choice toward larger, probabilistic rewards, whereas D-3 receptors appear to exert opposing effects on this form of decision making.