These data provide converging evidence supporting the possibility that NOPR activation may result in particularly beneficial anti-stress and anxiolytic-like effects when the CRF system is activated. This view is supported by gene expression data showing that exposure to stressful conditions, such as alcohol withdrawal or intracranial CRF administration, leads to up-regulated NOPR expression in the BNST, which may explain in part the enhanced efficacy of N/OFQ to produce anti-stress effects under these conditions (Martin-Fardon et al., 2010; Rodi et al., 2008).
