Adrenergic regulation of the hypothalamic-pituitary-adrenal axis under basal and social stress conditions.

The significance of adrenergic neurons and anterior pituitary and hypothalamic adrenergic receptors in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by corticotropin releasing hormone (CRH) and vasopressin (AVP) was investigated under basal conditions and after three-days crowding stress in conscious rats. In nonstressed rats the corticosterone response to phenylephrine, an alpha 1-adrenergic receptor agonist, was totally abolished or considerably reduced by prazosin, an alpha 1-receptor antagonist, when both those drugs were given ip or icv, respectively. The corticosterone response to ip isoproterenol, a beta-adrenergic agonist, was abolished by icv or ip pretreatment with propranolol, a beta-adrenergic receptor antagonist. These results indicate involvement of functional alpha 1-adrenoceptors in the hypothalamus and anterior pituitary corticotrops and pituitary beta-adrenoceptors in stimulation of the HPA axis. AVP given ip was almost as potent as CRH in stimulating corticosterone secretion. The stimulatory effect of AVP given ip or icv on corticosterone secretion was significantly diminished by propranolol, but not prazosin or yohimbine, indicating an involvement of beta-adrenergic receptors. The specific noradrenergic neurotoxin DSP-4, given ip 11 days before the experiment, considerably diminished the hypothalamic noradrenaline (NA) level but did not influence the resting and icv CRH- or AVP-stimulated corticosterone secretion. In nonstressed rats CRH further enhanced significantly the DSP-4-elicited fall in hypothalamic NA, whereas AVP almost totally prevented that decrease. In stressed rats CRH considerably antagonized the DSP-4-induced decrease in the hypothalamic NA level while AVP did not affect that decrease. The CRH- and AVP-elicited changes in hypothalamic NA were not correlated with changes in corticosterone secretion. Tree-day crowding stress did not affect the CRH-induced corticosterone secretion, whereas it considerably reduced the AVP-evoked corticosterone response. These results indicate that pituitary and hypothalamic adrenergic receptors are significantly involved in the AVP- and CRH-induced HPA axis stimulation, but the hypothalamic NA level, though modified by these peptides, does not significantly influence the HPA response.