Disorders associated with compulsive seeking of rewards, like binge-eating, are associated with abnormalities of the prefrontal cortex in humans, which is analogous to the prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) in rodents. Although studies have examined the role of the mPFC in drug seeking behaviors, studies examining natural reward seeking behaviors (i.e. food and sucrose) are often unclear and contradictory. This dissertation aims to characterize the role of the PL and IL mPFC in operant sucrose seeking behaviors. We used pharmacological and chemogenetic tools to selectively inactivate the PL, IL and PL-nucleus accumbens (NAc) NAc during Fixed Ratio 1 (FR1), extinction, and cue-induced reinstatement. Furthermore, we describe the role of PL projections to the NAc in both highly-motivated rats (food restricted) and low-motivated rats (free fed) in operant sucrose seeking behaviors. Our results demonstrate that the IL subregion of the mPFC plays a role in the execution of reward seeking behaviors during extinction (i.e. well entries) and cue-induced reinstatement (i.e. nose poking). Additionally, our results demonstrate that the PL plays a role in inhibiting reward seeking during FR1 (i.e. nose pokes and rewarded well entries). However, the PL seems to play a role in promoting reward seeking during extinction (i.e. nose poking and well entries). We also observed that inactivating PL-NAc in food restricted rats during extinction and cue-induced reinstatement suppresses behaviors that do not result in reward delivery (i.e., inactive lever presses). In free fed rats, PL-NAc inhibits reward seeking behaviors (i.e. initiated trials) during cue-induced reinstatement. Our findings support our claim that the mPFC and its projections differentially control reward seeking behaviors depending on the behavioral (e.g., FR1, extinction, or cue-induced reinstatement) and motivational context (e.g., level of satiety) of animals. Understanding the function of the mPFC will give insight to understand and develop specialized therapies to treat and cure disorders like binge-eating, as well as other diseases associated with the mPFC, like substance use disorders.