Study on the treatment of depression in terms of the spontaneous activity, ACTH and THmRNA -Efficacy of CRF binding protein, α-helical CRF and imipramine-

点击翻译按钮获取中文摘要

Purpose : This research was attempted to investigate whether both imipramine and corticotropine releasing factor (CRF) antagonists attenuate the increased function of hypothalamo-pituitary-adrenal (HPA) axis and noradrenaline (NA) synthesis in the locus coeruleus (LC) neurons of the stress-induced depressin-model rats. Methods : Adult rats were exposed to a forced walking stress for two weeks to produce animals with low spontaneous wheel-running activity, and high concentration of plasma ACTH and corticosterone. Imipramine (8mg/kg/day) and saline were intrapeitoneally injected to the depression-model rats for 20 days measuring spontaneous activity followed by decapitation to examine plasma ACTH and corticosterone as well as the expression of tyrosine hydroxylase (TH) mRNA in LC.α-helical (αh) CRF (10μg/day), astressin (10μg/day) : CRF antagonists, CRF (5μg/day) and saline were injected into LC of the other model rats for three days followed by the examination of activity, ACTH, corticosterone and THmRNA Results : 1. Imipramine enhanced the spontaneous activity, but lowered the concentration of ACTH and corticosterone, and the expression of THmRNA.2. αhCRF and astressin also lowered the concentration of ACTH and corticosterone. In these cases the spontaneous activity and THmRNA decreased on the next day of the last injection, but increased two weeks later. 3. The effects of CRF on the behavior and those biological markers were completely opposite to the results of treatment with CRF antagonists. These findings suggest that CRF antagonists as well as antidepressants attenuate the HPA function and NA synthesis in LC neurons which stay in a rest for a while, then rebound the synthesis that induces spontaneous activity.