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The Journal of Neuroscience, November 15, 1999, 19(22):10098-10106

Expression of _1b Adrenoceptor mRNA in Corticotropin-Releasing Hormone-Containing Cells of the Rat Hypothalamus and Its Regulation by Corticosterone

Heidi E. W. Day, Serge Campeau, Stanley J. Watson Jr, and Huda Akil

Mental Health Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0720

Considerable evidence supports a role for brainstem adrenergic and noradrenergic inputs to corticotropin-releasing hormone (CRH) cells of the hypothalamic paraventricular nucleus (PVN), in the control of hypothalamic-pituitary-adrenocortical (HPA) axis function. However, little is known about specific adrenoceptor (ADR) subtypes in CRH-containing cells of the PVN. Here we demonstrate, using dual in situ hybridization, that mRNA encoding _1b ADR is colocalized with CRH in the rat PVN. Furthermore, we confirm that these _1b ADR mRNA-containing cells are stress-responsive, by colocalization with c-fos mRNA after restraint, swim, or immune stress.

To determine whether expression of _1b ADR mRNA is influenced by circulating glucocorticoids, male rats underwent bilateral adrenalectomy (ADX) or sham surgery, and were killed after 1, 3, 7, or 14 d. In situ hybridization revealed levels of _1b ADR mRNA were increased in the PVN 7 and 14 d after ADX, but were not altered in the hippocampus, amygdala, or dorsal raphe. Additional rats underwent ADX or sham surgery and received a corticosterone pellet (10 or 50 mg) or placebo for 7 d. Corticosterone replacement (10 mg) reduced the ADX-induced increase in PVN _1b ADR mRNA to control levels, whereas 50 mg of corticosterone replacement resulted in a decrease in PVN _1b ADR mRNA as compared with all other groups. Furthermore, levels of plasma corticosterone were significantly correlated (inverse relationship) with _1b ADR mRNA in the PVN.

We conclude that _1b ADR mRNA is expressed in CRH-containing, stress-responsive cells of the PVN and is highly sensitive to circulating levels of corticosterone. Because activation of the _1B adrenoceptor is predominantly excitatory within the brain, we predict that this receptor plays an important role in facilitation of the HPA axis response.

Key words: adrenergic; adrenoceptor; HPA axis; stress; CRH; hypothalamus; paraventricular nucleus; in situ hybridization; adrenalectomy; glucocorticoid; corticosterone

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Copyright © 1999 Society for Neuroscience  0270-6474/99/192210098-09$05.00/0

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