Hypersecretion of corticotropin-releasing factor (CRF) has been hypothesized to occur in depression. To investigate CRF receptor (CRFR) response to the increased production of CRF in chronically stressed rats, we measured by in situ hybridization the expression of CRFR mRNA in the locus coeruleus (LC) concomitant with measuring plasma adrenocorticotropin (ACTH). The expression of both CRFR mRNA in the LC and the plasma level of ACTH increased significantly in "depression-model rats" which exhibit reduced activity following exposure to 14 days forced walking stress (FWS), but not in "spontaneous recovery rats" whose activity was restored after the long-term stress. These results suggest that the LC neurons continue to be stimulated by CRF, and that the hypothalamic-pituitary-adrenal (HPA) axis is hyperfunctioning in the depression-model rats.