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 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.
Footnotes
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Send reprint requests to: Nick E. Goeders, Ph.D., Department of Pharmacology & Therapeutics, LSU Medical Center, P.O. Box 33932, 1501 Kings Highway, Shreveport, LA 71130-3932. E-mail:ngoede{at}lsumc.edu
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↵1 This work was supported by United States Public Health Service Grants DA06013 and DA05836–01 from the National Institute on Drug Abuse.
- Abbreviations:
- HPA
- hypothalamo-pituitary-adrenal
- CRF
- corticotropin releasing factor
- ACTH
- adrenocorticotropic hormone
- LR
- low responder
- HR
- high responder
- EFS
- electric footshock
- MR
- mineralocorticoid receptor
- GR
- glucocorticoid receptor
- VEH
- vehicle
- CORT
- corticosterone
- ALDO
- aldosterone
- DEX
- dexamethasone
- ANOVA
- analysis of variance
- DA
- dopamine
- Received March 3, 1998.
- Accepted May 18, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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