Corticotropin-releasing hormone and its type 1 high-affinity receptor (CRHR1) are widely distributed throughout the brain. Together, they orchestrate the neuroendocrinological and behavioral adaptation to stress. Using conditional mutant mice, Refojo et al. found that CRHR1s on glutamatergic neurons in the amygdala and hippocampus are specifically involved with anxiety. However, CRHR1s on dopamine neurons in the midbrain had an opposing effect on anxiety via the regulation of dopamine release in the prefrontal cortex.
D. Refojo, M. Schweizer, C. Kuehne, S. Ehrenberg, C. Thoeringer, A. M. Vogl, N. Dedic, M. Schumacher, G. von Wolff, C. Avrabos, C. Touma, D. Engblom, G. Schütz, K.-A. Nave, M. Eder, C. T. Wotjak, I. Sillaber, F. Holsboer, W. Wurst, J. M. Deussing, Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1. Science 333, 1903–1907 (2011). [Abstract] [Full Text]