Figure 6.

Putative schematic flow of mechanism in the ventromedial prefrontal cortex (vmPFC) and basolateral nucleus of the amygdala (BLA) underlying stress-induced extinction deficits. In the vmPFC, stress has been shown to cause excess glutamate and associated dendritic hypotrophy and downregulation of glutamate receptors. These adaptations could lead to loss of vmPFC modulation of the amygdala and a resulting impairment in extinction that may be prevented by stimulating NMDA receptors using, eg, d-cycloserine. In the BLA, GR downregulation and anandamide depletion is seen after stress, which could in turn lead to reduced engagement of noradrenergic transmission and deficient extinction. There may be multiple points of intervention to reverse this cascade, including stimulating GRs or elevating anandamide with hydrocortisone and FAAH inhibitors, respectively, or blocking α2-adrenoceptors with yohimbine to increase BLA noradrenaline. BLA, basolateral amygdala; NE, norepinephrine; GR, glucocorticoid receptor; vmPFC, ventromedial prefrontal cortex.