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 wa s studied in control and stressed rats receiving i.c.v. injections of the a lpha1-adrenergic agonist, methoxamine, or the alpha1- antagonist, prazosin. 2. Plasma ACTH increased significantly 60 min and 4 hr after a single injec tion of methoxamine (100 mug, 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 singl e injection and by 96% after repeated injections. 3. CRH mRNA levels in the PVN increased by 131% after repeated injections f or 24 hr, but were unchanged 4 hr after a single injection. Central alpha1- adrenergic blockade with prazosin did not prevent the increases in CRH mRNA following 4 hr of acute stress, but significantly reduced the increases ob served 24 hr after an i.c.v. injection of 75 mug of colchicine or after rep eated i.p. hypertonic saline injections every 8 hr. 4. These studies demonstrate that while alpha1-adrenergic receptors contrib ute to longterm increases of CRH mRNA levels in the PVN during prolonged st ress, other factors are likely to be involved in the stimulation of CRH mRN A following acute stimulation.