Dissociable Contributions by Prefrontal D1 and D2 Receptors to Risk-Based Decision Making

Abstract

Choices between certain and uncertain rewards of different magnitudes have been proposed to be mediated by both the frontal lobes and the mesocorticolimbic dopamine (DA) system. In rats, systemic manipulations of DA activity or inactivation of the medial prefrontal cortex (PFC) disrupt decision making about risks and rewards. However, it is unclear how PFC DA transmission contributes to these processes. We addressed this issue by examining the effects of pharmacological manipulations of D 1 and D 2 receptors in the medial (prelimbic) PFC on choice between small, certain and large, yet probabilistic rewards. Rats were trained on a probabilistic discounting task where one lever delivered one pellet with 100% probability, and the other delivered four pellets, but the probability of receiving reward decreased across blocks of trials (100, 50, 25, 12.5%). D 1 blockade (SCH23390) in the medial PFC decreased preference for the large/risky option. In contrast, D 2 blockade (eticlopride) reduced probabilistic discounting and increased risky choice. The D 1 agonist SKF81297 caused a slight, nonsignificant increase in preference for the large/risky lever. However, D 2 receptor stimulation (quinpirole) induced a true impairment in decision making, flattening the discounting curve and biasing choice away from or toward the risky option when it was more or less advantageous, respectively. These findings suggest that PFC D 1 and D 2 receptors make dissociable, yet complementary, contributions to risk/reward judgments. By striking a fine balance between D 1 /D 2 receptor activity, DA may help refine these judgments, promoting either exploitation of current favorable circumstances or exploration of more profitable ones when conditions change.

Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

“…This in turn may facilitate cognitive functions, such as flexibility and task switching, as supported by recent in vivo measures of DA during cognitive tasks (St Onge et al, 2011) and behavioral observations (Floresco and Magyanar, 2006;Armbruster et al, 2012;Stelzel et al, 2013). Thus, by differentially modulating attractor landscapes in mPFC, monoamines may regulate the balance between opposing cognitive requirements .…”

“…Although AMPH is a drug of abuse and can induce mania and psychosis at high doses, it has also been shown to improve attention or vigilance and as therapeutic intervention in the treatment of a number of neuropsychiatric disorders (Sulzer et al, 2005). In humans, AMPH improves working memory, recall, and attention at low doses (Mattay et al, 1996(Mattay et al, , 2000(Mattay et al, , 2003Servan-Schreiber et al, 1998;Barch and Carter, 2005) but causes memory impairments at higher doses (Krystal et al, 2005;Tipper et al, 2005).…”

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

“…Such attendance to gains rather than loss are also seen in BD euthymic patients administered the DA D 2 /D 3 receptor agonist pramipexole (Burdick et al, 2014). In rats, DA D 1 and D 2 receptor contributions to win-stay/lose-shift strategies have been assessed during reward unpredictability (St Onge et al, 2011). The lack of punishment or varied reward levels in this reward probability task limits direct comparison to these data, but highlights how this mouse IGT paradigm can be used to examine the neural contribution to such reduced safe-stays and increased safe-shifts.…”

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

“…According to this view, the antagonist actions of eticlopride at (possibly) post-synaptic D 2 receptors may have facilitated learning from unsuccessful decisions to chase, raising the response threshold for further chasing behavior. The absence of any effects upon loss-chasing following SCH23390 suggests that D 1 receptor activity, although implicated in probabilistic choice (St Onge et al, 2011), makes only limited contributions to loss-chasing.…”

“…Converging evidence implicates the activity of midbrain dopamine neurones, and its innervated forebrain sites, in the representation of risk and uncertainty (St Onge et al, 2011), and also in the internal framing of choice outcomes as involving gains or losses relative to some reference point (De Martino et al, 2006). However, while the above findings indicate that both serotonin and dopamine activity support the cognitive and affective processes likely to be involved in loss-chasing behavior, their role in this central feature of gambling has not been properly specified.…”