Effects of stressor controllability on transcriptional levels of c-fos, Arc, and brain-derived neurotrophic factor in mouse amygdala and medial prefrontal cortex.

Controllability is an important factor in determining stress outcomes. Uncontrollable stress is associated with the development of psychopathology such as post-traumatic stress disorder, whereas controllable stress is associated with adaptive stress responses and positive outcomes. In this study, we investigated how controllability affects poststress neurobiology by assessing transcriptional levels of activity-dependent genes in medial prefrontal cortex (mPFC) and amygdala, regions important in mediating stress outcomes. Mice were subjected to either escapable shock (ES) or yoked inescapable shock (IS) as models of controllable and uncontrollable stress, respectively. Immediately (0 h) or at 2 h after shock training (20 trials; 0.5 mA, 5.0 s maximum duration; 1.0 min interstimulus interval), mice were killed, and we interrogated expression levels of the immediate-early genes, c-fos and Arc, and a delayed primary response gene, brain-derived neurotrophic factor, in mPFC, amygdala, and somatosensory cortex (a control region), using real-time reverse transcription quantitative PCR (RT qPCR). We found ES-associated up-regulation of brain-derived neurotrophic factor in amygdala as well as in mPFC. IS suppressed c-fos in mPFC (0 h) but induced more Arc in amygdala (2 h) in comparison with ES. Freezing, an index of fear memory, and serum level corticosterone, an index of the stress response, did not differ between mice trained with ES or IS. The data are discussed with respect to the potential functional involvements of the amygdala and mPFC in mediating differential outcomes of controllable and uncontrollable stress.