Administration of glucocorticoid agonists before or after initial extinction training

enhances extinction retention (Cai et al., 2006 and Yang et al., 2006), while blocking glucocorticoid activity impairs its consolidation (Barrett and Gonzalez-Lima, 2004 and Yang et al., 2006). Repeated glucocorticoid exposure, which leads to down-regulation of glucocorticoid release, has been shown to impair the retention of extinction memory (Gourley et al., 2008), suggesting that as in other forms of memory consolidation glucocorticoids play a HDAC inhibitor critical role in the storage of extinction learning. In humans, less work has assessed the effects of stress on extinction retention and retrieval. A recent investigation of extinction retrieval in women at different stages of their menstrual cycles revealed that extinction recall is better when preceded by stress in mid-cycling women with high estradiol status whereas the opposite was true of early cycling woman with low estradiol status (Antov and Stockhorst, 2014). This study highlights the important of expanding investigations to assess how endogenous sex and stress hormones may interact

and work synergistically or in opposition during emotional learning processes. We have recently demonstrated that inducing acute stress find more using the CPT in humans impaired extinction retrieval relative to non-stressed controls 24 h after intact fear learning and extinction training, irrespective of gender (Raio et al., 2014). Interestingly, conditioned responses across the extinction retrieval session were positively correlated with cortisol in both conditions. Although speculative, these results may be related to the not abundance of glucocorticoid receptors in both the amygdala and vmPFC, making these regions especially sensitive to stress. Given the vmPFC’s crucial role in extinction retrieval, dysfunction of this region or its connectivity to the amygdala is the most likely candidate by which stress might lead to extinction retrieval deficits. Consistent with this hypothesis,

recent work in humans has shown that functional connectivity between the amygdala and vmPFC is disrupted after CPT stress exposure (Clewett et al., 2013). Based on the animal and human work reviewed above, stress exposure appears to influence extinction processes differently depending on the phase at which stress is induced and extinction performance is assessed. Stress can impair the acquisition of extinction learning by potentially disrupting the inhibition conditioned fear responses. Likewise, stress hormones can impair the retrieval of extinction memory after intact learning. In contrast, stress and stress hormones can enhance the consolidation and storage of intact extinction training, leading to stronger retrieval when later tested.