Dopaminergic Modulation of Risk-Based Decision Making

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 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.

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

“…The apparent lack of effect of systemic nafadotride on impulsivity might result from these opposing actions in both the NAcbS and NAcbC, and not because an insufficient dose of nafadotride was used (see also Boulougouris et al (2008);St Onge and Floresco (2009)). It is also conceivable that brain regions other than the NAcb mediate in part the effects of the systemically administered drugs, potentially through opponent interactions between the PFC and striatum.…”

“…Nafadotride and aripiprazole were injected 20 min before behavioral testing according to a Latin-square design (veh, 1 and 3 mg/ kg) with a wash-out period of 1 week between both drugs. The doses were based on previously published research (Boulougouris et al, 2008;Nordquist et al, 2008;St Onge and Floresco, 2009). All drug testing was performed with sessions comprising a fixed ITI of 5 s.…”

Reduced Dopamine Transporter Functioning Induces High-Reward Risk-Preference Consistent with Bipolar Disorder

“…One key mechanism of DA homeostasis is its reuptake from the synaptic cleft into presynaptic nerve terminals by the DA transporter (DAT). Because several studies support an important role of DA in regulating risk-based decision making in rodents (Floresco et al, 2008;St Onge and Floresco, 2009), altered DAT functioning may contribute to abnormal decision making in individuals with BD. Supporting this assumption, polymorphisms in the DAT gene have been linked with BD (Greenwood et al, 2006;Pinsonneault et al, 2011), likely lowering functional DAT levels (Horschitz et al, 2005).…”

Impulsivity and Risk Taking in Bipolar Disorder and Schizophrenia

“…Impairments in these regions (eg, the orbitofrontal cortex in frontotemporal dementia) can lead to different neural mechanisms for increased impulsivity, as well as differential responses to dopaminergic medications. In the rat, D2 stimulation increased and D2 antagonism decreased risk taking (St Onge and Floresco, 2009). The results were attributed to the role of the nucleus accumbens, as part of the mesolimbic pathway (St Onge and Floresco, 2009).…”

“…In the rat, D2 stimulation increased and D2 antagonism decreased risk taking (St Onge and Floresco, 2009). The results were attributed to the role of the nucleus accumbens, as part of the mesolimbic pathway (St Onge and Floresco, 2009). In contrast, opposite results were found in a different rat model of risk-taking behavior (which included footshock punishment), with D2 receptor activation decreasing risktaking behavior and D2 antagonism attenuating this effect (Simon et al, 2011).…”