Research ReportDifferential roles of medial prefrontal subregions in the regulation of drug seeking

- The prefrontal cortex is important in regulating cognition and behavior.
- It plays an important role in seeking and taking, extinction, and reinstatement of drugs and natural rewards.
- Current theories of the relationship between rodent medial prefrontal cortex (mPFC) and behavior associate specific functions with specific subregions, e.g., dorsal mPFC plays a role in driving drug and reward seeking and ventral mPFC plays a role in inhibiting reward and drug seeking.
- Recent results challenge this framework and suggest alternate conceptualizations of how mPFC relates to drug/reward seeking.
- These results and alternate hypotheses connecting mPFC to drug and reward seeking are discussed as are important future directions necessary to develop a comprehensive understanding of the relationship between mPFC, reward seeking, and addiction.

The prefrontal cortex plays an important role in shaping cognition and behavior. Many studies have shown that medial prefrontal cortex (mPFC) plays a key role in seeking, extinction, and reinstatement of cocaine seeking in rodent models of relapse. Subregions of mPFC appear to play distinct roles in these behaviors, such that the prelimbic cortex (PL) is proposed to drive cocaine seeking and the infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction. This dichotomy of mPFC function may be a general attribute, as similar dorsal-ventral distinctions exist for expression vs. extinction of fear conditioning. However, other results indicate that the role of mPFC neurons in reward processing is more complex than a simple PL-seek vs. IL-extinguish dichotomy. Both PL and IL have been shown to drive and inhibit drug seeking (and other types of behaviors) depending on a range of factors including the behavioral context, the drug-history of the animal, and the type of drug investigated. This heterogeneity of findings may reflect multiple subcircuits within each of these PFC areas supporting unique functions. It may also reflect the fact that the mPFC plays a multifaceted role in shaping cognition and behavior, including those overlapping with cocaine seeking and extinction. Here we discuss research leading to the hypothesis that dorsal and ventral mPFC differentially control drug seeking and extinction. We also present recent results calling the absolute nature of a PL vs. IL dichotomy into question. Finally, we consider alternate functions for mPFC that correspond less to response execution and inhibition and instead incorporate the complex cognitive behavior for which the mPFC is broadly appreciated.This article is part of a Special Issue entitled Addiction circuits.