REPEATED STRESS-INDUCED ACTIVATION OF CORTICOTROPIN-RELEASING FACTOR NEURONS ENHANCES VASOPRESSIN STORES AND COLOCALIZATION WITH CORTICOTROPIN-RELEASING FACTOR IN THE MEDIAN-EMINENCE OF RATS

Stress-induced release of corticotropin-releasing factor (CRF) and vasopressin (AVP) was studied in rats by measuring the decline of CRF and AVP stores in the median eminence after blockade of fast axonal transport with colchicine (5-mu-g per rat intracisternally). Quantitative immunocytochemistry was used to detect changes in CRF(i) and AVP(i) in the external zone of the median eminence (ZEME) selectively. Immobilization stress induced a fast ACTH response to 1,000-2,000 pg/ml which was associated with a fall in both CRF(i) and AVP(i) of 34% during the first 30 min. This is followed by different time courses of further AVP(i) and CRF(i) depletion. In addition. In addition, we investigated the effect of repeated daily stress exposure on CRF(i) and AVP(i) in the ZEM 1 day after stress exposure. Repeated daily immobilization for 9 or 16 subsequent days did not affect the CRF(i) stores in the ZEME, but increased the AVP(i) stores to 161 +/- 13% and 218 +/- 11% respectively. Quantitative analysis of electron microphotographs of repeatedly handled rats showed a mean density of CRF positive profiles in the ZEME of 45.5 +/- 2.5 per 500-mu-m2 of which 25% also stained for pro-AVP-derived peptides. After 9 subsequent days of immobilization the total density of CRF-positive profiles remained unchanged, but the fraction of CRF swellings that also stained for pro-AVP-derived peptides increased approximately 2-fold. We conclude that (1) the secretion of AVP(i) and CRF(i) from the ZEME are independently controlled, indicating differential activation of AVP containing and AVP deficient CRF neurons during acute immobilization, and (2) repeated stress leads to plastic changes in hypothalamic CRF neurons resulting in increased AVP stores and colocalization in CRF nerve terminals.