The amygdaloid complex is a key region subserving stress responses and emotional behavior (Sah et al, 2003) and dysregulation of GABAergic signaling in the basolateral complex of the amygdala has been suggested to contribute to the pathophysiology of affective disorders (Quirk and Gehlert, 2003). Thus, this region is a candidate structure subserving the interactions between stress and exacerbation of mental illness. The basolateral complex contains high levels of CB1 receptors (Katona et al, 2001), and has been shown to express functional eCB signaling at inhibitory synapses (Marsicano et al, 2002; Zhu and Lovinger, 2005). We have earlier shown that restraint stress causes an increase in the concentration of 2-AG within the amygdaloid region (Patel et al, 2005b; Rademacher et al, 2008); an effect that exhibits sensitization on repeated exposure. Stress-induced activation of eCB signaling also has an important role in habituation of active and innate stress– response behaviors (Kamprath et al, 2006; Patel et al, 2005b). These data suggest that adaptations in 2-AG signaling in the amygdala could contribute to behavioral and emotional alterations that occur in response to chronic stress (Patel and Hillard, 2008), however, the synaptic mechanisms subserving these effects are not known.
