CONTRASTING EFFECTS OF CENTRAL ALPHA-1-ADRENOCEPTOR ACTIVATION ON STRESS-RESPONSIVE AND STRESS-NONRESPONSIVE SUBPOPULATIONS OF CORTICOTROPIN-RELEASING HORMONE NEUROSECRETORY-CELLS IN THE RAT

Stimulation of the rat hypothalamopituitary-adrenal axis during stress involves activation of central alpha1-adrenergic receptors. The subpopulation of corticotropin-releasing hormone (CRH) neurosecretory cells that contains vasopressin (VP) is selectively activated by several types of stress (immobilization, hypoglycemia, and intracerebroventricular, i.c.v., colchicine), and is located in a catecholamine-rich area of the hypothalamic paraventricular nucleus. Therefore, we tested the hypothesis that the CRH+/VP+ subpopulation is selectively activated by central alpha1-adrenergic receptors. The al-agonist methoxamine or vehicle alone was injected i.c.v. after habituation of rats to daily injections of vehicle through a chronic i.c.v. cannula. Activation of the CRH+/VP+ and CRH+/VP- subpopulations was measured by quantifying depletion of neurosecretory vesicles from immunocytochemically identified axons in the external zone of the median eminence. The habituated, vehicle-injected sham control group had normal levels of plasma ACTH and corticosterone, but possessed a significantly higher proportion of VP-containing CRH axons than naive animals. This change is similar to what was observed previously in rats subjected to repeated daily stress. I.c.v. methoxamine caused elevations of plasma ACTH and corticosterone and significant depletions of vesicles from the CRH+/VP+ axons at 1 and 2 h after injection, compared to the sham control group. The CRH+/VP- axons, however, displayed significant accumulations of neurosecretory vesicles at the same times after 300 mug methoxamine, compared to the sham control group. After 100 mug methoxamine, there was no change in the CRH+/VP- axons, compared to the sham control group. We interpret the accumulation of vesicles in the VP-deficient CRH neurosecretory axons after 300 mug i.c.v. methoxamine to reflect inhibition of this subpopulation after central alpha1-adrenergic receptor activation. The results demonstrate for the first time that central catecholamines induce release of both CRH and VP in the portal capillary plexus. These findings support the hypothesis that stress induces release of catecholamines from axons projecting to the paraventricular nucleus, thus activating alpha1-adrenergic receptors that selectively stimulate the VP-containing subpopulation of CRH neurosecretory cells.