Dopaminergic Modulation of Risk-Based Decision Making

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 34; no. 3; pp. 681 - 697
• Main Authors: ONGE, Jennifer R. St, FLORESCO, Stan B
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-02-2009
• Subjects: Adult and adolescent clinical studies; Amphetamines; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Benzamides - pharmacology; Benzazepines - pharmacology; Benzopyrans - pharmacology; Biological and medical sciences; Brain research; Bromocriptine - pharmacology; Conditioning, Operant - drug effects; Decision making; Decision Making - drug effects; Decision Making - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dextroamphetamine - pharmacology; Dopamine; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Dopamine D2 Receptor Antagonists; Gambling; Medical sciences; Naphthalenes - pharmacology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuropharmacology; Organic mental disorders. Neuropsychology; Oxazines - pharmacology; Parkinson's disease; Pharmacology. Drug treatments; Piperazines - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Pyridines - pharmacology; Pyrroles - pharmacology; Pyrrolidines - pharmacology; Rats; Rats, Long-Evans; Receptors, Dopamine D1 - agonists; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D3 - agonists; Receptors, Dopamine D3 - antagonists & inhibitors; Receptors, Dopamine D4 - agonists; Receptors, Dopamine D4 - antagonists & inhibitors; Reinforcement Schedule; Restless legs syndrome; Risk; Salicylamides - pharmacology; Canada; Amphetamine derivatives; Nervous system diseases; Dopamine; Parkinson's disease; CNS stimulant; Decision making; Psychotropic; D3 receptors; Parkinson disease; amphetamine; gambling; Catecholamine; Gambling game; D3 Dopamine receptor; Cerebral disorder; Discounting; D2 Dopamine receptor; Central nervous system disease; Risk factor; Neurotransmitter; Amfetamine; D2 receptors; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2008.121

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.