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Department of Physiology and Program in Neuroscience, University of California, San Francisco, California 94143-0444
Address all correspondence and requests for reprints to: Dr. Mary F. Dallman, Department of Physiology, Box 0444, University of California, San Francisco, California 94143-0444. E-mail: dallman{at}itsa.ucsf.edu.
When allowed to drink sucrose, bilaterally adrenalectomized (ADX) rats exhibit normal weight gain, food intake, sympathetic neural activity, and ACTH compared with sham-ADX rats. Furthermore, ADX rats drinking sucrose have normal corticotropin-releasing factor (CRF) mRNA throughout brain. In ADX rats without sucrose, all of these variables are abnormal. Systemic corticosterone (B) replacement also restores these variables in ADX rats to normal. To test whether B acts centrally, we infused B or saline intracerebroventricularly into ADX rats under basal conditions and after repeated restraint. Rats were exposed to no stress or 3 h/d restraint for 3 d. Body weights and food and fluid intakes were measured. Brains were analyzed using immunocytochemistry against glucocorticoid receptors (GR) and CRF. Intracerebroventricular B blocked the positive effects of sucrose on metabolism, increased basal ACTH concentrations, and augmented ACTH responses to restraint on d 3. B-infused rats exhibited nuclear GR staining in perirhinal cortex, hippocampus, and hypothalamic paraventricular nuclei, showing that infused B spreads effectively. CRF staining in the paraventricular nucleus of the hypothalamus was higher in B- than in saline-infused rats. We conclude that under basal conditions B acts systemically, but not in the brain, to restore metabolism and neuropeptides after adrenalectomy. By contrast, tonic GR occupancy in brain initiates metabolic and ACTH responses characteristic of stress.
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