When eCBs are released from the postsynaptic cell they diffuse in a retrograde fashion to activate presynaptic CB1 receptors, which in turn inhibits presynaptic release of neurotransmitters (Chhatwal and Ressler, 2007; Howlett, 2005; Lafenetre et al., 2007; Pertwee, 2005). In rodents it has been suggested that during extinction learning activation of vmPFC CB1 receptors induces neuronal plasticity, which subsequently increases inhibition on brain areas involved in the expression of conditioned fear responses (e.g. amygdala) (Lin et al., 2009) and HPC CB1 receptor activation enhances glutamatergic neurotransmission, which may support long-term extinction memory formation (consolidation) (de Oliveira Alvares et al., 2008). We are currently investigating the role of cannabinoids on the retention of extinction memory and its effect on the underlying neural circuits in humans using a similar Pavlovian fear conditioning-extinction paradigm coupled with fMRI.
