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

• Published in: The Journal of pharmacology and experimental therapeutics 1998-10, Vol.287 (1), p.72-80
• Main Authors: Mantsch, J R, Saphier, D, Goeders, N E
• Format: Article
• Language: English
• Subjects: Adrenal Glands - drug effects; Aldosterone - pharmacology; Animals; Body Weight - drug effects; Cocaine - administration & dosage; Corticosterone - blood; Corticosterone - pharmacology; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Male; Organ Size - drug effects; Rats; Rats, Wistar; Receptors, Glucocorticoid - agonists; Reinforcement (Psychology); Self Administration; Thymus Gland - drug effects
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1016/S0022-3565(24)37765-1

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.