CRF-receptor1 modulation of the dopamine projection to prelimbic cortex facilitates cognitive flexibility after acute and chronic stress.

Stress reduces cognitive flexibility and dopamine D1 receptor-related activity in the prelimbic cortex (PL), effects hypothesized to depend on reduced corticotropic releasing factor receptor type 1 (CRFr1) regulation of dopamine neurons in the ventral tegmental area (VTA). We assessed this hypothesis in rats by examining the effect of chronic unpredictable restraint stress (CUS), mild acute stress, or their combination on cognitive flexibility, CRFr1 expression in the VTA and D1-related activity in PL. In Experiment 1, rats received either CUS or equivalent handling for 14 days before being trained to press two levers to earn distinct food outcomes.