Dopamine D1/D2 Receptor Activity in the Nucleus Accumbens Core But Not in the Nucleus Accumbens Shell and Orbitofrontal Cortex Modulates Risk-Based Decision Making.

BACKGROUND: It is well known that brain dopamine (DA) signals support risk-based decision making; however, the specific terminal regions of midbrain DA neurons through which DA signals mediate risk-based decision making are unknown. METHODS: Using microinfusions of the D1/D2 receptor antagonist flupenthixol, we sought to explore the role of D1/D2 receptor activity in the rat orbitofrontal cortex (OFC) and core and shell regions of the nucleus accumbens (AcbC and AcbS, respectively) in the regulation of risky choices. A risk-discounting task was used that involves choices between a certain small-reward lever that always delivered 1 pellet or a risky large-reward lever which delivered 4 pellets but had a decreasing probability of receiving the reward across 4 subsequent within-session trial blocks (100%, 50%, 25%, 12.5%). To validate task sensitivity to experimental manipulations of DA activity, we also examined the effects of systemic amphetamine and flupenthixol. RESULTS: Systemic amphetamine increased while systemic flupenthixol reduced risky choices. Results further demonstrate that rats that received intra-AcbC flupenthixol were able to track increasing risk associated with the risky lever but displayed a generally reduced preference for the risky lever across all trial blocks, including in the initial trial block (large reward at 100%). Microinfusions of flupenthixol into the AcbS or OFC did not alter risk-based decision making. CONCLUSIONS: Our data suggest that intra-AcbC D1/D2 receptor signaling does not support the ability to track shifts in reward probabilities but does bias risk-based decision making. That is, it increased the rats' preference for the response option known to be associated with higher risk-related costs.

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

Considerable evidence has implicated dopamine (DA) signals in target regions of midbrain DA neurons such as the medial prefrontal cortex or the core region of the nucleus accumbens in controlling risk-based decision-making. However, to date little is known about the contribution of DA in the orbitofrontal cortex (OFC) and the medial shell region of the nucleus accumbens (AcbS) to risk-based decision-making. Here we examined in rats the effects of 6-hydroxydopamine-induced DA depletions of the OFC and AcbS on risky choice using an instrumental two-lever choice task that requires the assessment of fixed within-session reward probabilities that were shifted across subsequent sessions, i.e., rats had to choose between two levers, a small/certain lever that delivered one certain food reward (one pellet at p = 1) and a large/risky lever that delivered a larger uncertain food reward with decreasing probabilities across subsequent sessions (four pellets at p = 0.75, 0.5, 0.25, 0.125, 0.0625). Results show that systemic administration of amphetamine or cocaine increased the preference for the large/risky lever. Results further demonstrate that, like sham controls, rats with OFC or AcbS DA depletion were sensitive to changes in probabilities for obtaining the large/risky reward across sessions and displayed probabilistic discounting. These findings point to the view that the basal capacity to evaluate the magnitude and likelihood of rewards associated with alternative courses of action as well as long-term changes of reward probabilities does not rely on DA input to the AcbS or OFC.

Intact risk-based decision making in rats with prefrontal or accumbens dopamine depletion.

The medial prefrontal cortex (mPFC) and the core region of the nucleus accumbens (AcbC) are key regions of a neural system that subserves risk-based decision making. Here, we examined whether dopamine (DA) signals conveyed to the mPFC and AcbC are critical for risk-based decision making. Rats with 6-hydroxydopamine or vehicle infusions into the mPFC or AcbC were examined in an instrumental task demanding probabilistic choice. In each session, probabilities of reward delivery after pressing one of two available levers were signaled in advance in forced trials followed by choice trials that assessed the animal's preference. The probabilities of reward delivery associated with the large/risky lever declined systematically across four consecutive blocks but were kept constant within four subsequent daily sessions of a particular block. Thus, in a given session, rats need to assess the current value associated with the large/risky versus small/certain lever and adapt their lever preference accordingly. Results demonstrate that the assessment of within-session reward probabilities and probability discounting across blocks were not altered in rats with mPFC and AcbC DA depletions, relative to sham controls. These findings suggest that the capacity to evaluate the magnitude and likelihood of rewards associated with alternative courses of action seems not to rely on intact DA transmission in the mPFC or AcbC.

Motivational states influence effort-based decision making in rats: the role of dopamine in the nucleus accumbens.

Decision-making policies are subject to modulation by changing motivational states. However, so far, little is known about the neurochemical mechanisms that bridge motivational states with decision making. Here we examined whether dopamine (DA) in the nucleus accumbens core (AcbC) modulates the effects of motivational states on effort-based decision making. Using a cost-benefit T-maze task in rats, we examined the effects of AcbC DA depletions on effort-based decision making, in particular on the sensitivity of effort-based decision making to a shift from a hungry to a sated state. The results demonstrated that, relative to sham controls, rats with AcbC DA depletion in a hungry as well as in a sated state had a reduced preference for effortful but large-reward action. This finding provides further support for the notion that AcbC DA regulates how much effort to invest for rewards. Importantly, our results further revealed that effort-based decision making in lesioned rats, as in sham controls, was still sensitive to a shift from a hungry to a sated state; that is, their preferences for effortful large-reward actions became lower after a shift from a restricted to a free-feeding regimen. These finding indicate that AcbC DA is not necessarily involved in mediating the effects of a shift in motivational state on decision-making policies.