Differential influence of corticosterone and dexamethasone on schedule-induced polydipsia in adrenalectomized rats

Previous studies have shown that adrenalectomy prevents the normal acquisition of schedule-induced polydipsia (SIP), while corticosterone (CORT) administration reinstates this behavior in adrenalectomized (ADX) rats. These studies investigated which corticosteroid receptor is responsible for mediating CORT effects on SIP. In Experiment I the effects of dexamethasone (DEX) and CORT on the acquisition of SIP were studied. DEX and CORT pellets (respectively 15 mg and 200 mg) were implanted subcutaneously in ADX rats. CORT but not DEX replacement was able to reinstate SIP in ADX rats. Because DEX binds almost exclusively to glucocorticoid receptors (GRs), while CORT binds to both GRs and mineralocorticoid receptors (MRs), results from Experiment I indicated that occupancy of GRs alone is not sufficient for SIP acquisition. In Experiment II CORT pellets of different concentrations (1, 10, 50, 200 mg) were implanted in ADX rats in order to determine whether MRs alone, or a combination of GRs and MRs are required for SIP reinstatement. Results from Experiment II showed that the 1 and 10 mg CORT pellets were not able to reinstate SIP in adrenalectomized rats, while animals implanted with 50 or 200 mg pellets did exhibit the behavior. These results indicate that occupancy of both MRs and GRs is required for SIP acquisition.