The role of the medial prefrontal cortex in delay discounting

Abstract

Increased delay discounting (DD) has been associated with and is theorized to contribute to alcoholism and substance abuse. It is also been associated with numerous other mental disorders and is believed to be a trans-disease process (i.e., a process that occurs in and contributes to multiple different pathologies). Consequently insights gained from studying DD are likely to apply to many different diseases. Studies on the neurobiological underpinnings of DD have two main interpretations. The first interpretation is that two different neurobehavioral systems exist, one favoring delayed rewards (executive system) and one favoring immediate rewards (impulsive system), and the system with the greater relative activation determines choice made by an individual. Alternatively, a single valuation system may exist. This system integrates different information about outcomes and generates a value signal that then guides decision making. Preclinical investigations have steered clear of these two different interpretations and rather focused on the role of individual structures in DD. One such structure, the rat mPFC, may generate an outcome representation of delayed rewards that is critically involved in attributing value to delayed rewards. Moreover, there is evidence indicating the rat mPFC may correspond to the primate dlPFC, an executive system structure. The current body of work set about testing the hypotheses that the mPFC is necessary for attributing value to delayed rewards and that decreasing the activity in an executive system area, and thus the executive system, shifts inter-temporal preference towards immediate rewards. To this end the rat mPFC was inactivated using an hM4Di inhibitory designer receptor exclusively activated by designer drugs (DREADD; experiment 1) or microinjections of tetrodotoxin (TTX; experiment 2) while animals completed an adjusting amount DD task. Activation of the hM4Di inhibitory DREADD receptor caused a decrease in DD, opposite of what was predicted. Electrophysiological recordings revealed a subpopulation of neurons actually increased their firing in response to hM4Di receptor activation, potentially explaining the unpredicted results. Microinjections of TTX to completely silence neural activity in the mPFC failed to produce a change in DD. Together both results indicate that mPFC activity is capable of manipulating but is not necessary for DD and the attribution of value to the delayed reward. Consequently, a secondary role for the rat mPFC in DD is proposed in line with single valuation system accounts of DD. Further investigations determining the primary structures responsible for sustaining delayed reward valuation and how manipulating the mPFC may be a means to decrease DD are warranted, and continued investigation that delineates the neurobiological processes of delayed reward valuation may provide valuable insight to both addiction and psychopathology.