Effects of chronic stress on anterior pituitary and brain corticotropin-releasing factor receptors

Abstract

[ 125I]Corticotropin-releasing factor binding was measured in membrane homogenates prepared from the anterior pituitary, frontal cortex, motor cortex, somatosensory cortex, mesolimbic area (olfactory tubercle and nucleus accumbens), caudate putamen, hypothalamus, midbrain, and cerebellum from control and chronically stressed rats. The stressor consisted of 3 or 14 days of around-the-clock intermittent foot-shock (approximately one trial per 5-min frequency) that could be avoided or escaped on 90% of the trials presented by pulling a ceiling chain. Plasma corticosterone levels were almost doubled in stressed rats following 3 days of chronic stress and remained significantly elevated in rats stressed for 14 days as compared to controls. Plasma corticotropin levels were similar in controls and stressed animals in both the 3- and 14-day experiments. [ 125I]Corticotropin-releasing factor binding was decreased in anterior pituitary and frontal cortex following 3 ways of chronic stress; binding affinity of anterior pituitary membranes was not different between control and stressed animals. [ 125I]Corticotropin-releasing factor binding was similar in control and 3-day-stressed animals in the other brain areas examined. After 14 days of chronic stress, hypothalamic [ 125I]corticotropin-releasing factor binding was decreased in stressed rats as compared to control animals but no other differences were seen. The decrease in the apparent number of anterior pituitary corticotropin-releasing factor receptors following 3 days of stress may be due, in part, to increased plasma corticosterone levels and/or increased corticotropin-releasing factor secretion during that time. The downregulation of frontal cortex and hypothalamic corticotropin-releasing factor receptors, however, is more likely to be primarily in response to sustained stress-induced corticotropin-releasing factor release at those sites.