, 2007). However, MLN0128 higher levels of noradrenaline release as seen during stress exposure is thought to engage lower affinity alpha-1 and beta-adrenergic receptors subtypes that impair prefrontal function (Birnbaum et al., 1999 and Ramos et al., 2005) but strengthen activity in the amygdala (McGaugh, 2004). Glucocorticoids can also function in a synergistic manner with noradrenaline to exacerbate its effects in PFC (Ferry et al., 1999, Roozendaal et al., 2004, Grundemann et al., 1998 and Arnsten, 2009).

Therefore, it is possible that both noradrenergic and glucocorticoid responses to acute stress, and the interacting influence they exert in the brain, serve as a potential mechanism for the impact of stress on the cognitive control of fear. The observation that even a mild stressor can render cognitive emotion regulation less effective is especially striking considering that these techniques are used pervasively in clinical contexts to treat an array

of psychological disorders. Cognitive reappraisal and restructuring comprise some of the primary principles underlying for Cognitive-Behavioral Therapy (CBT), a therapeutic technique often referred to CX-5461 in vitro as the ‘gold-standard’ for treating an array of psychological dysfunction, including anxiety and trauma-related disorders (Beck and Emery, 1985, Beck and Dozois, 2011, Butler et al., 2006 and Hofmann and Smits, 2008). However, we note that our stress manipulation took place after only one session of Resveratrol training, whereas the majority of CBT treatment plans are instituted over an extended period of time (e.g., 12–24 weeks) (Butler et al., 2006). Stress likely has more limited effects of cognitive emotion regulation as training continues and is practiced over time, therefore we do not argue that cognitive regulation does not have utility in clinical settings, only that its vulnerability

to acute stress in the early stages of training should be considered. Additionally, it is important to note that there are multiple components to CBT for which our study was not designed or capable of testing, such the social support garnered from therapeutic relationships, as well as a broad range of restructuring techniques inherent in CBT, which include encouraging patients to recognize and correct automatic thoughts that may be irrational or maladaptive to promote more adaptive emotional responses. It is possible the combination of all of these components might lead to CBT being more resistant to stress even while the specific reappraisal components use in our task are notably impaired under stress. Although the majority of fear regulation techniques involve changing the value associated with an aversive stimulus, adopting a course of action or inhibiting a response in order to avoid an aversive outcome can also control fear responses.