Role of alpha-1-adrenergic receptors in the regulation of corticotropin-releasing hormone mRNA in the paraventricular nucleus of the hypothalamus during stress.

1. The role of alpha1-adrenergic receptors on CRH mRNA levels in the PVN was studied in control and stressed rats receiving i.c.v. injections of the alpha1-adrenergic agonist, methoxamine, or the alpha1- antagonist, prazosin. 2. Plasma ACTH increased significantly 60 min and 4 hr after a single injection of methoxamine (100 microg, i.c.v.). No desensitization of this response was observed after repeated injections every 6 hr for 24 hr. Concomitantly, POMC mRNA in the anterior pituitary increased by 25% at 4 hr after a single injection and by 96% after repeated injections. 3. CRH mRNA levels in the PVN increased by 131% after repeated injections for 24 hr, but were unchanged 4 hr after a single injection. Central alpha-adrenergic blockade with prazosin did not prevent the increases in CRH mRNA following 4 hr of acute stress, but significantly reduced the increases observed 24 hr after an i.c.v. injection of 75 microg of colchicine or after repeated i.p. hypertonic saline injections every 8 hr. 4. These studies demonstrate that while alpha1-adrenergic receptors contribute to longterm increases of CRH mRNA levels in the PVN during prolonged stress, other factors are likely to be involved in the stimulation of CRH mRNA following acute stimulation.