Emotional learning is extremely important for the survival of an individual. However, once acquired, emotional associations are not always expressed. The regulation of emotional responses under different environmental conditions is essential for mental health. Indeed, pathologic feelings of fear and anxiety are defining features of many serious psychiatric illness, including post-traumatic stress disorder (PTSD) and specific phobias. The simplest form of regulation of emotional responses is extinction, in which the conditioned response to a stimulus decreases when reinforcement (stimulus) is omitted. In addition to modulating basal anxiety states, recent studies suggest an important role for the endocannabinoid (eCB) and glucocorticoid systems in the modulation of emotional states and extinction of aversive memories in animals. The purpose of this review is to briefly outline the animal models of fear extinction and to describe how these have been used to examine the potential of extinction enhancing agents which specifically alter the eCB and glucocorticoid systems. Pharmacological manipulations of these systems by agents such as cannabinoid or glucocorticoid agonists can enhance the extinction process and avoid the retention of memories which have the potential to trigger trauma. A better understanding of these findings through animal models highlights the possibilities of using combined extinction enhancing agents in exposure-based psychotherapies for anxiety disorders related to inappropriate retention of aversive memories. This article is part of a special issue entitled ‘Cognitive Enhancers’.

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