Receptor-Specific Modulation of Risk-Based Decision Making by Nucleus Accumbens Dopamine

Abstract

The nucleus accumbens (NAc) serves as an integral node within cortico-limbic circuitry that regulates various forms of cost-benefit decision making. The dopamine (DA) system has also been implicated in enabling organisms to overcome a variety of costs to obtain more valuable rewards. However, it remains unclear how DA activity within the NAc may regulate decision making involving reward uncertainty. This study investigated the contribution of different DA receptor subtypes in the NAc to risk-based decision making, assessed with a probabilistic discounting task. In well-trained rats, D1 receptor blockade with SCH 23,390 decreased preference for larger, uncertain rewards, which was associated with enhanced negative-feedback sensitivity (ie, an increased tendency to select a smaller/certain option after an unrewarded risky choice). Treatment with a D1 agonist (SKF 81,297) optimized decision making, increasing choice of the risky option when reward probability was high, and decreasing preference under low probability conditions. In stark contrast, neither blockade of NAc D2 receptors with eticlopride, nor stimulation of these receptors with quinpirole or bromocriptine influenced risky choice. In comparison, infusion of the D3-preferring agonist PD 128,907 decreased reward sensitivity and risky choice. Collectively, these results show that mesoaccumbens DA refines risk-reward decision biases via dissociable mechanisms recruiting D1 and D3, but not D2 receptors. D1 receptor activity mitigates the effect of reward omissions on subsequent choices to promote selection of reward options that may have greater long-term utility, whereas excessive D3 receptor activity blunts the impact that larger/uncertain rewards have in promoting riskier choices.

A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

“…Therefore, we think it is justified to state that the deficits in reversal learning, probabilistic discounting and punished reward taking evoked by chemogenetic mesoaccumbens stimulation is the result of increased DA signaling in the NAc. Reversal learning impairments have previously been reported after systemic or intra-NAc treatment with a DA D2 receptor agonist in rats and humans [47][48][49] , whereas probabilistic discounting seems to be dependent on DA D1 rather than D2 receptor stimulation in the NAc 50 . Together, this suggests that the behavioral effects of mesoaccumbens hyperactivity observed here rely on stimulation of both DA receptor subtypes, depending on the task structure.…”

Adolescent Risk Taking, Cocaine Self-Administration, and Striatal Dopamine Signaling

“…Interestingly, a recent report showed that ventral striatal quinpirole administration had no effect on choice behavior in a probability-discounting task, which is similar to the RDT but in which the 'cost' associated with the large reward is risk of reward omission (Stopper et al, 2013). The authors attributed the lack of quinpirole effects to a greater role for D3 than D2 receptors in this task.…”

Orbitofrontal or accumbens dopamine depletion does not affect risk-based decision making in rats

“…Furthermore, in a risk discounting task that involved withinsession shifts of large reward probabilities, inactivation of the AcbS reduced the bias toward larger-magnitude rewards (Stopper & Floresco, 2011), suggesting that the AcbS may play a subtle and task-dependent role in risk-based decisionmaking. DA signals in the whole Acb support risk-based decision-making (Stopper, et al, 2013); however, the selective contribution of DA signals in the AcbS has not been investigated so far. Our data suggest that AcbS DA input may not play a major role to support the capacity to evaluate magnitude and likelihood of rewards associated with different levers, at least in a probabilistic choice task that involves probability discounting across sessions with fixed within-session reward probabilities.…”

“…Our data suggest that AcbS DA input may not play a major role to support the capacity to evaluate magnitude and likelihood of rewards associated with different levers, at least in a probabilistic choice task that involves probability discounting across sessions with fixed within-session reward probabilities. However, it is possible that AcbC DA depletion, similar to intra-Acb infusion of DA receptor antagonists (Stopper, et al, 2013), alters risky choice in tasks that involve within-session shifts of reward probabilities (Cardinal & Howes, 2005;St Onge & Floresco, 2009) demanding more complex cognitive processes, i.e., a persistent evaluation and updating of the current values associated with the available response options.…”

“…For instance, DA in the mPFC and Acb plays a crucial role in risk-based decision-making in complex instrumental tasks that demand an assessment of short-term within-session changes in reward probabilities associated with different levers (St Onge, et al, 2011;Stopper, Khayambashi, & Floresco, 2013). By contrast, DA in the mPFC and AcbC does not support risk-based decision-making in simpler instrumental choice tasks involving fixed within-session reward probabilities that were shifted across subsequent sessions .…”