Prefrontal Dopamine D1 and D2 Receptors Regulate Dissociable Aspects of Decision Making via Distinct Ventral Striatal and Amygdalar Circuits

Mesocortical dopamine (DA) regulates a variety of cognitive functions via actions on D1 and/or D2 receptors. For example, risk/reward decision making is modulated differentially by these two receptors within the prefrontal cortex (PFC), with D-2 receptors enabling flexible decision making and D-1 receptors promoting persistence in choice biases. However, it is unclear how DA mediates opposing patterns of behavior by acting on different receptors within the same terminal region. We explored the possibility that DA may act on separate networks of PFC neurons that are modulated byD(1) or D-2 receptors and in turn interface with divergent downstream structures such as the basolateral amygdala (BLA) or nucleus accumbens (NAc). Decision making was assessed using a probabilistic discounting task in which well trained male rats chose between small/certain or large/risky rewards, with the odds of obtaining the larger reward changing systematically within a session. Selective disruption of D-1 or D-2 modulation of separate PFC output pathways was achieved using unilateral intra-PFC infusions of DA antagonists combined with contralateral inactivation of the BLA or NAc. Disrupting D-2 (but not D-1) modulation of PFC -> BLA circuitry impaired adjustments in decision biases in response to changes in reward probabilities. In contrast, disrupting D-1 modulation of PFC -> NAc networks reduced risky choice, attenuating reward sensitivity and increasing sensitivity to reward omissions. These findings reveal that mesocortical DA can facilitate dissociable components of reward seeking and action selection by acting on different functional networks of PFC neurons that can be distinguished by the subcortical projection targets with which they interface.