Vol. 287, Issue 1, 72-80, October 1998

Corticosterone Facilitates the Acquisition of Cocaine Self-Administration in Rats: Opposite Effects of the Type II Glucocorticoid Receptor Agonist Dexamethasone¹

John R. Mantsch, David Saphier and Nick E. Goeders

Departments of Pharmacology and Therapeutics (J.R.M., D.S., N.E.G.) and Psychiatry (N.E.G.), Louisiana State University Medical Center, Shreveport, Louisiana

The effect of corticosterone on the acquisition of cocaine-seeking behavior was investigated in rats using ascending dose-response curves for intravenous cocaine self-administration. Rats pretreated daily with corticosterone (2.0 mg/kg i.p.) acquired cocaine self-administration at a lower dose compared with vehicle-treated controls. In contrast, daily corticosterone pretreatment did not alter food-maintained responding. Cocaine self-administration was not affected by the type I (mineralocorticoid) receptor agonist, aldosterone (100 µg/kg). However, rats treated with the type II (glucocorticoid) receptor agonist, dexamethasone (10 or 100 µg/kg) did not acquire self-administration at any dose tested. The 100 µg/kg dose of dexamethasone attenuated food-reinforced behavior and decreased body weight, but these effects were not observed with the 10 µg/kg dose. Dexamethasone dose-dependently attenuated the plasma corticosterone response to self-administered infusions or intraperitoneal injections of cocaine, indicating that the ability of dexamethasone to block cocaine-induced corticosterone secretion may have contributed to its effects on self-administration. Administration of aldosterone (100 µg/kg) together with 10 µg/kg dexamethasone restored self-administration to the level of vehicle-treated rats, suggesting that type I receptor occupation by corticosterone may be required for the acquisition of this behavior. These results indicate that stress-induced corticosterone secretion may provide a substrate through which stressors interact with cocaine reinforcement. Additionally, the finding that dexamethasone blocks the acquisition of cocaine self-administration may be relevant to the development of novel approaches to the treatment of cocaine addiction.