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Abstract

Psychopharmacological studies have implicated the mesolimbic dopamine (DA) system in the mediation of cost/benefit evaluations about effort-related costs associated with larger rewards. However, the role of DA in risk-based decision making remains relatively unexplored. The present study investigated how systemic manipulations of DA transmission affect risky choice assessed with a probabilistic discounting task. Over discrete trials, rats 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 D₁ (SCH23390) or D₂ (eticlopride) receptors antagonists. Blockade of either of these receptors alone induced risk aversion. Conversely, stimulation of D₁ (SKF81297) or D₂ (bromocriptine) receptors also increased risky choice. In contrast, activation of D₃ receptors with PD128,907 induced risk aversion. Likewise, D₃ antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D₄ receptors did not reliably alter patterns of choice. These findings indicate that DA plays a critical role in mediating risk-based decision making, where increased activation of D₁ and D₂ receptors biases choice towards larger, probabilistic rewards, whereas D₃ receptors appear to exert opposing effects on this form of decision making.