Stress-Induced Redistribution of Corticotropin-Releasing Factor Receptor Subtypes in the Dorsal Raphe Nucleus

BackgroundThe stress-related neuropeptide corticotropin-releasing factor (CRF) is involved in determining behavioral strategies for responding to stressors, in part through its regulation of the dorsal raphe (DR)-serotonin (5-HT) system. CRF1 and CRF2 receptor subtypes have opposing effects on this system that are associated with active versus passive coping strategies, respectively.MethodsImmunoelectron microscopy and in vivo single-unit recordings were used to assess CRF receptor distribution and neuronal responses, respectively, in the DR of stressed and unstressed rats.ResultsHere we show that in unstressed rats CRF1 and CRF2 are differentially distributed within DR cells, with CRF1 being prominent on the plasma membrane and CRF2 being cytoplasmic. Stress experience reverses this distribution, such that CRF2 is recruited to the plasma membrane and CRF1 tends to internalize. As a consequence of this stress-induced cellular redistribution of CRF receptors, neuronal responses to CRF change from inhibition to a CRF2-mediated excitation.ConclusionsGiven evidence that CRF1 and CRF2 activation are associated with distinct behavioral responses to stress, the stress-triggered reversal in receptor localization provides a cellular mechanism for switching behavioral strategies for coping with stressors.