PARTICIPATION OF ALPHA-1-ADRENERGIC RECEPTORS IN THE SECRETION OF HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE DURING STRESS

The role of alpha-1-adrenergic receptors in the secretion of corticotropin-releasing hormone (CRH) during stress was studied by immunohistochemical analysis of the CRH content of the median eminence (ME) after intracerebroventricular (icv) administration of the alpha-1-adrenergic agonist, methoxamine, or the antagonist, prazosin, in rats pretreated with colchicine. Immunohistochemical staining was performed by the peroxidase technique on 40-mu-m free-floating sections using a polyclonal antibody specific for CRH. In the first experimental model, rats were implanted with icv cannulae and adapted to the experimental conditions by daily handling and icv injection of artificial CSF. Colchicine (75-mu-g) was administered through the cannulae 6 h before the experiment, conditions in which axonal transport was blocked with little change in basal immunostaining. Two hours after immobilization stress or a single injection of methoxamine (100-mu-g, icv), there was a marked decrease in CRH immunoreactivity throughout the ME, reflecting release of the neuropeptide into the portal circulation. The decrease in CRH immunostaining following immobilization was largely prevented by icv injection of the alpha-1-adrenergic antagonist, prazosin. In the second experimental model, rats were sacrificed 48 h after icv colchicine injection, conditions in which colchicine acts as a stressor and causes marked depletion of irCRH from the ME. This chronic effect of colchicine was also partially prevented by administation of prazosin, 400-ng injection 5 min prior to colchicine, followed by a continuous icv minipump infusion of prazosin, indicating that alpha-1-adrenergic stimulation contributes to the action of colchicine. In addition, the increase in the number and immunodensity of CRH cell bodies in the paraventricular nucleus typically observed following 48 h colchicine treatment was markedly reduced by prazosin administration, suggesting that alpha-1-adrenergic stimulation causes an increase in peptide synthesis as well as release. These results indicate that central alpha-adrenergic mechanisms are an important component in the regulation of hypothalamic CRH secretion during stress.