The prefrontal cortex (PFC) plays an important role in several forms of cost-benefit decision making. Its contributions to decision making under risk of explicit punishment, however, are not well understood. A rat model was used to investigate the role of the medial PFC (mPFC) and its monoaminergic innervation in a Risky Decision-making Task (RDT), in which rats chose between a small, "safe" food reward and a large, "risky" food reward accompanied by varying probabilities of mild footshock punishment. Inactivation of mPFC increased choice of the large, risky reward when the punishment probability increased across the session ("ascending RDT"), but decreased choice of the large, risky reward when the punishment probability decreased across the session ("descending RDT"). In contrast, enhancement of monoamine availability via intra-mPFC amphetamine reduced choice of the large, risky reward only in the descending RDT. Systemic administration of amphetamine reduced choice of the large, risky reward in both the ascending and descending RDT; however, this reduction was not attenuated by concurrent mPFC inactivation, indicating that mPFC is not a critical locus of amphetamine's effects on risk taking. These findings suggest that mPFC plays an important role in adapting choice behavior in response to shifting risk contingencies, but not necessarily in risk-taking behavior per se.

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