Roman high- (RHA) and low- (RLA) avoidance rats are selected and bred for rapid versus non-acquisition of two-way, active avoidance behavior in a shuttle box. They also show a number of other behavioral differences which appear to be essentially related to emotional factors, the RLA rats being emotionally more sensitive. The ACTH secretory response to stressors is also augmented in RLA rats. We thus raised the question whether the expression of corticotropin-releasing factor (CRF) and vasopressin (VP), two neurohormones exerting a synergistic action on ACTH release from corticotropic cells, is different in the two strains. Steady-state mRNA levels were examined in the parvicellular neurons of the paraventricular nucleus under basal conditions and 4 h after a single 8-min exposure to an open-field stressor. In situ hybridization histo-chemistry with 35S-labeled oligonucleotide probes was followed by quantitative cell by cell autoradiography. When basal CRF and VP mRNA levels were compared in the two lines, we found that the RLA rats had a significantly higher VP-labeling density than the RHA rats. No difference was found for CRF mRNA. During open-field exposure, we observed behavioral differences paralleled by elevated corticosterone compatible with an increased emotional response in RLA rats. Open-field exposure produced a significant increase in CRF but not VP mRNA in both RHA and RLA rats (by 43 and 57%, respectively). These results suggest that differences in basal VP expression in CRF neurons may participate in the mechanisms underlying the hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis in the emotionally more sensitive RLA rats. Thus, these Swiss sublines of RHA-RLA rats might provide a useful model to study the role of genetic predisposition and superimposed environmental factors on the regulation or dysregulation of the HPA axis.

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