Chronic Variable Stress Induces Avolition and Disrupts Corticoaccumbens Encoding of Approach Cues
Date of Award
Doctor of Philosophy (PhD)
Wheeler, Robert A.
Disorders in the ability to process, evaluate, and interact with rewards are hallmarks of a range of mental illnesses. Such disorders are multi-faceted and arise from altered activity throughout diffuse brain regions. Chronic variable stress (CVS) is an oft-used tool for modeling reward-related disorders in preclinical research because it impairs the function of multiple brain regions and causes a range of severe hedonic and motivational deficits. While much research has focused on the former, the latter is poorly characterized. A panel of behavioral tests was used to characterize the effect of CVS exposure on different facets of reward related behaviors in Sprague-Dawley rats. In a subset of animals, in vivo electrophysiology was used to assess the impact of CVS on reward encoding in a primary reward processing region, the nucleus accumbens (NAc). Behavioral deficits occurred in motivational, rather than hedonic, domains, and stress altered the encoding of primary rewards in the Shell subregion of the NAc, an area responsible for encoding value. The prelimbic region of the prefrontal cortex (PL) is known to be sensitive to stress and responsive to reward-predictive cues. The extent to which this area encodes the incentive value of cues has not been characterized. Pavlovian autoshaping is a behavior in which trained animals transfer the incentive value of a primary reward to an associated cue. In vivo electrophysiological recordings of single units in the PL of Sprague-Dawley rats demonstrated that this region was attuned to incentivized cues in the autoshaping paradigm. A projection pathway from the PL targeting the NAc Core (NAcC) subregion has a significant role in promoting motivated approach. However, little is known about how activity in this pathway (1.) changes during associative learning to encode incentivized cues or (2.) may be altered by stress. An intersectional fiber photometry approach used in male Sprague Dawley rats engaged in autoshaping demonstrated that the rapid acquisition of conditioned approach was associated with cue-induced PL-NAcC activity. Prior stress reduced both cue-directed behavior and associated cortical activity. These results support the interpretation that stress disrupts reward processing by altering the attribution of incentive to associated cues.