Whereas the pharmaceutical industry should develop blood–brain-barrier-penetrating, selective CRHR antagonists, preclinical research is required to identify suitable animal models of depression because, for example, the forced swimming test, although it has demonstrated some validity in predicting the antidepressant potential of compounds, has been repeatedly questioned as a test to phenotype animals as ‘depressed’ [69]. Here, CRHR1 is linked to major depressive disorder.