Differential effects of prior stress on conditioned inhibition of fear and fear extinction.

Resistant and generalized fear are hallmark symptoms of Post-Traumatic Stress Disorder (PTSD). Given PTSD is highly comorbid with addiction disorders indicates a maladaptive interaction between fear and reward circuits. To investigate learning processes underlying fear, reward and safety, we trained male rats to discriminate among a fear cue paired with footshock, a reward cue paired with sucrose and an explicit safety cue co-occurring with the fear cue in which no footshocks were delivered. In an attempt to emulate aspects of PTSD, we pre-exposed male rats to a stressor (15 unsignaled footshocks) before training them to fear, reward and safety cues, and subsequent fear and reward extinction. Prior stress did not produce any significant impairments on conditioned inhibition to a safety cue compared to non-stressed controls. However, in subsequent fear extinction, prior stress profoundly impaired fear reduction to an extinguished fear cue. Prior stress also significantly reduced reward seeking to a reward-associated cue throughout training. Together, our data show that prior stress did not affect conditioned inhibition of fear to the same extent as impairing fear extinction. These results have interesting implications on how safety circuits are organized and impacted by stress, leading to possibly new avenues of research on mechanisms of stress disorders, such as PTSD.