Lack of glucocorticoids enhances the early activation of the medullary catecholaminergic cell groups triggered by restraint stress.

We have investigated whether the stress-induced activation of the medullary catecholaminergic neurons, that was shown previously to provide the main central activation input to the hypothalamo-pituitary-adrenocortical axis during an immobilization stress, is sensitive to circulating corticosteroids. Experiments were carried out on adrenalectomized rats that were first maintained on corticosterone in the drinking water for 5 days following surgery and then switched to corticosterone-free water 15 h before stress application. Some of the latter animals were injected with dexamethasone. Activation of the brainstem Catecholaminergic neurons was estimated by assaying 3,4-dihydroxyphenylacetic acid (DOPAC), a side metabolite of the noradrenaline and adrenaline biosynthesis pathway that was established previously as a reliable index of the activity of these neurons. In the so-called A(1) C(1) and A(2) C(2) Catecholaminergic groups of the medulla, lack of corticosterone under these experimental conditions did not modify the basal level of DOPAC but led to a further enhancement (+ 35% to 40%) of the approximately 2-fold increase in DOPAC content observed 15 min after the onset of the 5-min immobilization stress. No significant further enhancement of the stress-induced DOPAC increase was observed in the locus coeruleus. In these adrenalectomized rats, dexamethasone pretreatment prevented the enhancement of the stress-induced increase in DOPAC level observed in the medullary cell groups but did not abolish the response to stress. Lack of endogenous corticosteroids led to a 10-fold enhancement of the adrenocorticotropin increase following immobilization stress. Pretreatment with dexamethasone fully abolished the stress-induced increase in adrenocorticotropin plasma level. Our results show that circulating corticosteroids reduce the stress-induced activation of the medullary A(1) and A(2) C(2) groups i.e. those that contribute mainly to the catecholaminergic innervation of the hypothalamo-pituitary-adrenocortical axis within the hypothalamic paraventricular nuclei. However, since the feedback regulation of the central catecholaminergic systems is much less efficient than the feedback actually observed on the adrenocorticotropin secretion, we suggest that it is likely to play a minor physiological role in the overall feedback regulation exerted by circulating corticosteroids on the hypothalamo-pituitary-adrenocortical axis.