EDN1 and Anxiety: To validate the PSD phenotype in sub-chronic and chronic phases following stroke, we have followed best practice guidelines for testing mouse behavior, which includes using: (i) more than one behavioral test; (ii) using tests that have construct and face validity, as well as outcomes that are objective, reproducible and sensitive enough to detect a long-term deficit.56, 72 The ET-1-induced ischemic lesion of the left mPFC produced a significant anxiety phenotype detected in all four tests: EPM, OF, LD and NSF; and a behavioral despair phenotype in both the TST and FST.