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  • Title: Corticosterone facilitates the acquisition of cocaine self-administration in rats: opposite effects of the type II glucocorticoid receptor agonist dexamethasone.
    Author: Mantsch JR, Saphier D, Goeders NE.
    Journal: J Pharmacol Exp Ther; 1998 Oct; 287(1):72-80. PubMed ID: 9765324.
    Abstract:
    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.
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