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Delayed Punishment Decision-making Task

Brain regulates sensitivity to delayed punishment to improve treatments for substance use.

A fundamental characteristic of substance use disorder is ongoing drug use in the face of physical, financial, and legal consequences. One rationale for this poor decision-making is the delay between substance use and its negative outcomes. For example, heroin exposure can cause painful withdrawal symptoms, dependence, and extensive social/financial problems, but these outcomes often manifest long after substance use. Therefore, it is critical to understand how the brain regulates sensitivity to delayed punishment to improve biological and behavioral treatments for substance use. The Simon Lab in the Department of Psychology was recent awarded a grant from the National Institute of Drug Abuse that uses cutting edge chemogenetic manipulation to investigate the neurochemical brain circuits that mediate decision-making guided by delayed punishment.

Dr. Nicholas Simon,  associate professor of Psychology, and his graduate student colleagues developed the novel “Delayed Punishment Decision-making Task”, which reveals that rats, like humans, underestimate the negative value of delayed punishment during decision-making. Furthermore, the Simon lab observed that this “discounting” of delayed punishment is dependent on a brain region called the orbitofrontal cortex (OFC). However, the OFC does not function in a vacuum, instead receiving multiple inputs from distinct deep brain structures. This project will determine how specific modulatory inputs to OFC, the ventral tegmental area and locus coeruleus, regulate decision-making with both delayed and immediate punishment. This will be accomplished by inserting viral vectors containing Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) into specific areas within the rat brain, enabling both cell-type and circuit specific chemical manipulation of neural activity during decision-making behavior.

This project will provide unprecedented information on how specific brain circuits regulate sensitivity to both delayed and immediate punishment. The research team’s ultimate goal is to determine if direct manipulation of these understudied circuits can serve as a potential treatment to improve decision-making in substance use disorder.

For more information on this research, contact Simon at nwsimon@memphis.edu.