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In contrast to these findings, a conditional KO mouse for DOPr (Dlx-DOR) in forebrain GABAergic neurons showed a reduced level of anxiety compared to wild-type littermates, demonstrating that stimulation of DOPr in GABAergic neurons of the forebrain is anxiogenic (see Table 1) [62].
Taken together, the combined findings from these silencing, pharmacological, genetic, and neuroanatomical studies suggest that the stimulation of ENK transmission onto DOPr and/or MOPr might enhance the natural strategies to cope with stress.
Enkephalin Signaling through DOPr and MOPr, a Major Component of the Stress Resilience Circuitry
also studied in rats the effects of dominance status and housing conditions on the response to a DOPr agonist, SNC80 [74].
When considering only one neuropeptidergic system, the ENK acting through DOPr and MOPr, numerous implicated brain structures and circuits emerge (see Figure 1 for a schematic representation that we overlapped with the cartography of main connectivities known to be involved in stress response, fear, and resilience).
Caption: Figure 1: Cartography of main connectivities involved in fear, stress, and resilience, as well as demonstrated ENK pathways between areas and expression of ENK, MOPr, and DOPr. Pink circles represent brain regions of interest.