In addition to the role of a stress-induced decline in AEA signaling in regulation of the HPA axis, there is data to suggest that this reduction in AEA signaling may be involved in other effects of stress. Within the hippocampus, AEA signaling is known to promote cell proliferation as genetic deletion of FAAH has been found to significantly increase progenitor cell proliferation in the dentate gyrus (Aguado et al., 2005). As stress is known to produce a reduction in AEA signaling in this region, we sought to determine if this decline in AEA was involved in the reduction in cell proliferation that occurs in this region following exposure to stress. Our data demonstrate that administration of the AEA uptake inhibitor/FAAH inhibitor AM404 prior to stress exposure prevented the suppression of cell proliferation in the dentate gyrus following exposure to predator odor stress (Hill et al., 2006). These data indicate that one possible outcome of the reduction in AEA signaling following stress is a consequential reduction in cell proliferation in the hippocampus. It has yet to be determined if this decline in AEA following stress is involved in changes in other forms of neuroplasticity.
