As now published in Nature Genetics, the researcher at the Max Planck Institute of Psychiatry, Munich, in collaboration with the GSF Research Center, have been able to show by generating a mouse mutant with CRHR1-deficiency that the anxiogenic effect of CRH is mediated by the CRHR1 receptor. Indeed, these CRHR1-deficient mice show reduced stress hormone response (cortisol response) under acute stress conditions, and were less anxious in behavioral tests. In general, when wild-type mice are subjected to forced alcohol consumption and, subsequently, alcohol withdrawal conditions, they exhibit enhanced anxiogenic reactions. In contrast, CRHR1-deficient mice showed less anxiogenic behavior under alcohol withdrawal then wild-type mice. Thus by eliminating CRHR1 functions, anxiogenic behavior can be manipulated and probably other symptoms correlated with depression.
These findings have now led to the assumption that new drugs which suppress CRHR1 function might be able to reduce symptoms of depression and anxiety in patients. The clinical use of CRH-antagonists could therefore lead to a faster and more effective therapeutic response than classical antidepressants, and represents a completely new mode of action.