Neuropsycopharmacology (Link to full-length article)

Abstract

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 D1 (SCH23390) or D2 (eticlopride) receptor 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 reduced choice of the large/risky lever. Likewise, D3 antagonism with nafadotride potentiated the amphetamine-induced increase in risky choice. Blockade or stimulation of D4 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 D1 and D2 receptors biasing choice toward larger, probabilistic rewards, whereas D3 receptors appear to exert opposing effects on this form of decision making.

Commentary

In this study, we systematically assessed how pharmacological manipulations of dopamine transmission in rodents may alter cost/benefit decision making about risks and rewards using a probabilistic discounting task. Previous studies in humans and animals have indirectly implicated the dopamine system in these processes. For example, treatment with dopamine agonist therapy leads to the emergence of pathological gambling tendencies in some individuals. In this study, rats chose between two options, one that delivered a small/certain food reward, and another that larger yet probabilistic ("risky") reward. Under normal conditions, rats discount larger/risky rewards more often as the odds of obtaining them decrease within a session. We observed that increasing dopamine transmission with amphetamine, or selective D1 or D2 receptor agonists induce a marked increase in risky choice, whereas blocking these receptors induced risk aversion. In contrast, manipulations of D3 receptor activity induced effects opposite to those induced by D2 receptor agents.  Our findings indicate that increases or decreases in the fine balance of dopamine transmission can directly affect decisions about certain versus uncertain rewards.  We believe these findings provide novel insight into the perturbations in decision making observed in a number of neuropsychiatric disorders where disruptions in dopamine transmission is though to be a contributing factor.