Single or repeated mild stress increases synthesis and release of hypothalamic corticotropin-releasing factor

Abstract

The effect of a specific mild stress on the levels of corticotropin-releasing factor immunoreactivity (CRF-ir) in the hypothalamus of adult male rats was determined using a radioimmunoassay specific for rat CRF. A single 5 min restraint significantly increased CRF-ir in the median eminence 24 h later compared to appropriate controls ( P < 0.025), with no change detected earlier. Plasma ACTH, an indirect index of CRF release, was significantly elevated within 15 min ( P < 0.0025). Repetition of mild stress daily for 9 days ( P < 0.01), or a single episode of handling ( P < 0.05), both resulted in significantly increased CRF-ir in the whole hypothalamus 24 h later. Blockade of axonal transport by intracisternal colchicine decreased CRF-ir in the median eminence 24 h later ( P < 0.005). Inhibition of protein synthesis by anisomycin during a single 5 minute restraint resulted in significantly decreased CRF-ir in the median eminence 24 h later compared to vehicle-injected stressed rats ( P < 0.005) or to anisomycin-injected unstressed controls ( P < 0.025). These data show that mild stress increased net hypothalamic CRF content as a result of the balance between augmented synthesis and augmented release.