OPRK1 and major depressive disorder: KOR has been proposed to be involve in the stress system implicated in depression pathophysiology and was identified as an important component in depression and other psychiatric disorders characterized by reward dysfunction.[58, 59, 62] The development of KOR antagonists as potential antidepressants are mainly driven [63] by their antidepressant-like effects in in vivo studies.[64] The prototype of non-peptide KOR antagonist, nor-BNI, could produce antidepressant-like effects in both forced-swimming (FS) [65] and learned helplessness (LH) [66] assays in rodent models.