CHRONIC COLD IN ADRENALECTOMIZED, CORTICOSTERONE-(B)-TREATED RATS - FACILITATED CORTICOTROPIN RESPONSES TO ACUTE RESTRAINT EMERGE AS B INCREASES

Small elevations in corticosterone (B) administered exogenously exert potent inhibitory effects on both basal and stress-induced ACTH secret ion. However, under conditions of chronic stress with chronic elevatio ns in B, the hypothalamo-pituitary-adrenal system appears to balance t he negative feedback signal of B with central neural facilitation so t hat the system remains fully responsive to acute stressors. In these s tudies, we tested whether: 1) circulating B concentrations affect resp onses to acute restraint in rats exposed to 5 days at 5-7 C (cold), co mpared with room temperature (control); and 2) facilitated ACTH secret ion can be explained by increased CRF or vasopressin messenger RNA (mR NA) levels in the hypothalamic parvocellular paraventricular nuclei (P VN). Rats were adrenalectomized and supplied with B in doses that fixe d plasma B at constant levels between approximately 2 and 20 mu g/dl; rats were placed in cold or remained as controls. Increasing concentra tions of fixed B decreased basal ACTH similarly in both groups. By con trast, as B levels increased, ACTH responses to restraint also increas ed in cold vs. control rats. Semiquantitative analysis of CRF mRNA by in situ hybridization revealed decreases of similar magnitude in both groups with increasing fixed B. Vasopressin mRNA levels also decreased with increasing fixed B in both groups, but with slightly less sensit ivity to inhibition by B in cold exposed rats. Taken together, the dec reases in mRNA for these major ACTH neuropeptide secretogogues in the parvocellular PVN are unlikely to explain facilitated ACTH responses i n chronically stressed rats. We conclude that a brain site is stimulat ed by B that is proximal to the PVN; feedforward, positive effects of B are thus implicated in mediation of prior stress-induced facilitatio n of acute hypothalamo-pituitary-adrenal responses to stress.