Journal
NEUROPSYCHOPHARMACOLOGY
Volume 34, Issue 3, Pages 681-697Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2008.121
Keywords
D-2 receptors; amphetamine; D-3 receptors; gambling; Parkinson's disease; discounting
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Funding
- Canadian Institutes of Health Research
- Parkinson's Society Canada
- Natural Sciences and Engineering Research Council of Canada
- Michael Smith Foundation for Health Research
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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.
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