Lateral Orbitofrontal Cortex and Basolateral Amygdala Regulate Sensitivity to Delayed Punishment during Decision-making.

In real-world decision-making scenarios, negative consequences do not always occur immediately after a choice. This delay between action and outcome drives the underestimation, or "delay discounting", of punishment. While the neural substrates underlying sensitivity to immediate punishment have been well-studied, there has been minimal investigation of delayed consequences. Here, we assessed the role of lateral orbitofrontal cortex (LOFC) and basolateral amygdala (BLA), two regions implicated in cost/benefit decision-making, in sensitivity to delayed vs immediate punishment. The delayed punishment decision-making task (DPDT) was used to measure delay discounting of punishment in rodents. During DPDT, rats choose between a small, single pellet reward and a large, three pellet reward accompanied by a mild foot shock. As the task progresses, the shock is preceded by a delay that systematically increases or decreases throughout the session. We observed that rats avoid choices associated with immediate punishment, then shift preference toward these options when punishment is delayed. LOFC inactivation did not influence choice of rewards with immediate punishment, but decreased choice of delayed punishment. We also observed that BLA inactivation reduced choice of delayed punishment for ascending but not descending delays. Inactivation of either brain region produced comparable effects on decision-making in males and females, but there were sex differences observed in omissions and latency to make a choice. In summary, both LOFC and BLA contribute to the delay discounting of punishment and may serve as promising therapeutic targets to improve sensitivity to delayed punishment during decision-making.Negative consequences occurring after a delay are often underestimated, which can lead to maladaptive decision-making. While sensitivity to immediate punishment during reward-seeking has been well-studied, the neural substrates underlying sensitivity to delayed punishment remain unclear. Here, we used the Delayed Punishment Decision-making Task to determine that lateral orbitofrontal cortex and basolateral amygdala both regulate the discounting of delayed punishment, suggesting that these regions may be potential targets to improve decision-making in psychopathology.