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Neural and Behavioral Consequences of Drug Abuse During Decision-Making

Chronic drug use impairs brain function leading to persistent deficits in impulse control and decision-making.  Although much is known about structural and chemical changes that occur after long term drug abuse, it is still unclear how brain signals necessary for adaptive decision-making are affected. To address this issue, Dr. Roesch has spent his career recording neural activity from single brain cells as rats perform a variety of decision-making tasks with the overarching goal to elucidate how the brain controls behavior in both healthy animals and in animal models of disease. Ultimately, the goal is to rescue disrupted signals and restore behavior to normal levels.

To accomplish these goals, the Roesch lab trains rats to perform several different decision-making paradigms. In one such task, rats choose between two different options; either a large and small reward (sugar water) or between an immediate and delayed reward. Like humans, rats prefer immediate over delayed reward, even when the delayed reward is much larger. This behavior is referred to as impulsive choice or delay-discounting and is elevated in humans and rats exposed to drugs of abuse. Dr. Roesch was awarded a grant from National Institute on Drug Abuse (NIDA) to elucidate the neural mechanisms engaged during impulsive choice and how they are affected by chronic cocaine self-administration.
 
In addition to impulsive choice, behavioral deficits observed in addicts can be characterized as the inability to stop or inhibit an unwanted action. This type of impulsivity is known as motor impulsivity and is commonly assessed by the so-called stop-signal task. In this task, humans and rats are instructed to make a simple ‘GO’ response on 80% of trials (e.g. push a button). On these trials participants quickly develop the habit of rapidly responding without much thought. However, on 20% of trials, a ‘STOP’ cue instructs participants that they must withhold the action in order to perform the trial correctly.  Performance on this task is disrupted in several psychiatric disorders, including drug addiction and attention deficit hyperactivity disorder (ADHD). Recently, Dr. Roesch’s lab has shown that prenatal exposure to nicotine during pregnancy causes similar deficits in impulse control.  More importantly, these changes in behavior were correlated with a reduction in neural activity in the medial prefrontal cortex, a brain area thought to be critical for inhibitory control. This work is important because exposure to nicotine during pregnancy has been linked to several disorders including drug abuse and ADHD. Future studies will attempt to rescue behavior in prenatal nicotine exposed rats via artificial stimulation of the medial prefrontal cortex as a possible treatment strategy.
 
Matthew Roesch
Department of Psychology