Effect of central catecholamine depletion on 3H-dexamethasone binding in the dog.

Abstract

Dogs were bilaterally adrenalectomized (Adx) or sham adrenalectomized 2 weeks after the administration of 6-hydroxydopamine (6-OHDA) or saline-ascorbic acid vehicle directly into the third ventricle (3V). Hypothalamic and hippocampal cytosols were assayed in vitro for high affinity binding of 3H-dexamethasone (3H-DM). 6-OHDA treatment resulted in a significant reduction of norepinephrine concentration in the hypothalamus, but not in the hippocampus, when measured 2 weeks after the second dose. Treatment with this neurotoxin also caused a decrease in 3H-DM binding in the hypothalamus that was detectable after adrenalectomy. A statistically significant reduction in bound DM was not observed in the hypothalamus after 6-OHDA treatment of dogs with intact adrenals, perhaps because of a masking effect of endogenous corticosteroids. No change was observed in the hippocampus. Saturation analysis of binding data revealed the total maximum number of available binding sites in hypothalamic cytosol was lower after 6-OHDA treatment, compared to saline-injected controls. Calculated values for dissociation constants revealed no differences between dogs treated with Adx, saline and Adx, and 6-OHDA. The data support the suggestion that catecholamines may act, in part, by altering the specific binding of a glucocorticoid to its hypothalamic receptor.