Mouse anxiety: the power of knockout

The role of the neurokinine 1 receptors (NK1R) and its endogenous ligand, the neuropeptide substance P (SP) in the pathophysiology and treatment response of anxiety and depression has been controversial. In a new study, however, mice with a targeted inactivation of the NK1R show a phenotype that is associated with anxiety-related behaviors and stress responses. Since this behavioral phenotype was associated with an increase in serotonergic function, NK1R knockout mice represent a systematic model for advanced investigations of SP/NK1R and serotonin system interaction in anxiety responses. The availability of an increasing number of knockout mouse anxiety models as well as integration of emerging tools and technologies for genetic analysis will provide the groundwork for the genetic dissection of anxiety and related disorders.