Corticosterone facilitates the acquisition of cocaine self-administration in rats: opposite effects of the type II glucocorticoid receptor agonist dexamethasone. J Pharmacol Exp Ther 1998 Oct;287(1):72-80
Date
10/09/1998Pubmed ID
9765324Scopus ID
2-s2.0-0032463958 (requires institutional sign-in at Scopus site) 106 CitationsAbstract
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 microgram/kg). However, rats treated with the type II (glucocorticoid) receptor agonist, dexamethasone (10 or 100 microgram/kg) did not acquire self-administration at any dose tested. The 100 microgram/kg dose of dexamethasone attenuated food-reinforced behavior and decreased body weight, but these effects were not observed with the 10 microgram/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 microgram/kg) together with 10 microgram/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.
Author List
Mantsch JR, Saphier D, Goeders NEAuthor
John Mantsch PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adrenal GlandsAldosterone
Animals
Body Weight
Cocaine
Corticosterone
Dexamethasone
Dose-Response Relationship, Drug
Male
Organ Size
Rats
Rats, Wistar
Receptors, Glucocorticoid
Self Administration
Thymus Gland
