Chronic Stress Prevents Cortico-Accumbens Cue Encoding and Alters Conditioned Approach.

Chronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in male Sprague Dawley rats engaged in a Pavlovian autoshaping design to characterize the involvement of the PL-NAcC pathway in the typical acquisition of learned approach (directed at both the predictive cue and the goal), and its potential alteration by stress. Specifically, the hypothesis that neural activity in PL-NAcC would encode a Pavlovian approach cue and that prior exposure to chronic stress would disrupt both the nature of conditioned approach and the encoding of a cue that promotes approach was tested. Results of the study demonstrated that the rapid acquisition of conditioned approach was associated with cue-induced PL-NAcC activity. Prior stress both reduced cue-directed behavior and impaired the associated cortical activity. These findings demonstrate that prior stress diminishes the task-related activity of a brain pathway that regulates approach behavior. In addition, the results support the interpretation that stress disrupts reward processing by altering the incentive value of associated cues.SIGNIFICANCE STATEMENT Chronic stress causes hedonic and motivational deficits and disrupts the function of the PFC. A specific projection from the prelimbic region of the PFC to the nucleus accumbens core (PL-NAcC) promotes approach behavior and is a strong candidate for contributing to stress-induced disruptions in motivation. However, it is not known how activity in this pathway encodes cues that promote approach, and how this encoding may be altered by stress. Here we show that the rapid acquisition of conditioned approach is associated with cue-induced activity in the PL-NAcC pathway. Prior stress both reduces cue-directed behavior and impairs the associated cortical activity. These findings demonstrate that stress diminishes task-related activity in a brain pathway that regulates approach behavior.