Abstract
Corticotropin-releasing factor (CRF) and CRF-related neuropeptides are involved in the regulation of stress-related physiology and behavior. Members of the CRF family of neuropeptides bind to two known receptors, the CRF type 1 (CRF&sub1;) receptor, and the CRF type 2 (CRF&sub2;) receptor. Although the distribution of CRF&sub2; receptor mRNA expression has been extensively studied, the distribution of CRF&sub2; receptor protein has not been characterized. An area of the brain known to contain high levels of CRF&sub2; receptor mRNA expression and CRF&sub2; receptor binding is the dorsal raphe nucleus (DR). In the present study we investigated in detail the distribution of CRF&sub2; receptor immunoreactivity throughout the rostrocaudal extent of the DR. CRF&sub2; receptor-immunoreactive perikarya were observed throughout the DR, with the highest number and density in the mid-rostrocaudal DR. Dual immunofluorescence revealed that CRF&sub2; receptor immunoreactivity was frequently co-localized with tryptophan hydroxylase, a marker of serotonergic neurons. This study provides evidence that CRF&sub2; receptor protein is expressed in the DR, and that CRF&sub2; receptors are expressed in topographically organized subpopulations of cells in the DR, including serotonergic neurons. Furthermore, these data are consistent with the hypothesis that CRF&sub2; receptors play an important role in the regulation of stress-related physiology and behavior through actions on serotonergic and non-serotonergic neurons within the DR.