Original Article

Neuropsychopharmacology (2009) 34, 681–697; doi:10.1038/npp.2008.121; published online 30 July 2008

Dopaminergic Modulation of Risk-Based Decision Making

Jennifer R St Onge1 and Stan B Floresco1

1Department of Psychology and Brain Research Center, University of British Columbia, Vancouver, BC, Canada

Correspondence: Dr SB Floresco, Department of Psychology and Brain Research Center, University of British Columbia, 2136 West Mall, Vancouver, BC V6T 1Z4, Canada. Tel: +604 827 5313; Fax: +604 822 6923; E-mail: floresco@psych.ubc.ca

Received 30 May 2008; Revised 8 July 2008; Accepted 11 July 2008; Published online 30 July 2008.

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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.

Keywords:

D2 receptors, amphetamine, D3 receptors, gambling, Parkinson's disease, discounting

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