In the brain, CB1 receptors are densely localized within brain structures that are known to be critical for extinction learning, retention and successful retrieval of extinction memories (ventromedial prefrontal cortex [vmPFC] and hippocampus [HPC]) (Bouton et al., 2006; Corcoran et al., 2005; Kalisch et al., 2006; Mackie, 2005; Milad and Quirk, 2002; Milad et al., 2006; Milad et al., 2007; Myers and Davis, 2007; Ochsner and Gross, 2005; Phelps et al., 2004; Quirk and Beer, 2006; Quirk et al., 2006; Quirk et al., 2003; Quirk and Mueller, 2008). In humans, vmPFC activation during extinction recall and vmPFC thickness both correlate with magnitude of extinction retention (Hartley et al., 2011; Milad et al., 2005b; Milad et al., 2007; Phelps et al., 2004). In rats, cells within the infralimbic cortex (IL), a homologous structure to the human vmPFC, display robust CS-elicited activity during extinction recall which is inversely correlated with spontaneous recovery of fear CRs (Milad and Quirk, 2002). Similarly, the hippocampus (HPC) is associated with successful retrieval of extinction memory and is positively correlated with vmPFC activation during extinction recall in humans (Kalisch et al., 2006; Milad et al., 2007).
