Short-term enriched environment exposure facilitates fear extinction in adult rats: The NPY-Y1 receptor modulation

Neuropeptides have an important role in several psychiatric conditions. Among them, neuropeptide Y (NPY) seems to be essential to modulate some features of stress-related disorders. Post-traumatic stress disorder (PTSD), characterized by inappropriate fear generalization to safe situations may be modulated by NPY manipulation since this neuropeptide is involved in the promotion of coping with stress. Experimentally, coping strategies have been obtained after exposure in enriched environment (EE) rather than standard one. Thus, in the present study we aimed to assess whether short-term EE situation and NPY-Y1 receptor (Y1r) modulation may affect the extinction of contextual fear conditioning, an experimental approach to PTSD. Here we show that EE-rats have the contextual fear extinction facilitated, and this facilitation was reverted by central infusion of BIBO3304, a nonpeptide Y1r antagonist. In addition, protein analysis revealed an upregulation of hippocampal Y1r in conditioned EE-rats, but no changes were observed in EE-rats that were not conditioned. Our results demonstrated that protective properties of EE on fear extinction can be regulated, at least in part, by activation of NPY-signaling through Y1r within hippocampus, an area that plays a major role in contextual memories. Overall, the activation of Y1r is important to promote better and faster perception of self-location (context), and to reduce fear generalization in rats exposed to EE.