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Ketoconazole reduces low dose cocaine self-administration in rats
N E Goeders1, R L Peltier, G F Guerin
1Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130-3932, USA. ngoede@lsumc.edu
Drug and Alcohol Dependence
|August 10, 2000
Summary
Ketoconazole, an antifungal drug, reduced cocaine self-administration in rats by lowering corticosterone levels. This suggests ketoconazole may aid in treating cocaine abuse.
Area of Science:
- Pharmacology
- Neuroscience
- Addiction Research
Background:
- Ketoconazole is an antifungal medication with known effects on adrenocorticosteroid synthesis.
- Glucocorticoids, like corticosterone, play a role in reward pathways and addiction.
- Understanding drug interactions is crucial for developing effective addiction treatments.
Purpose of the Study:
- To investigate the effects of ketoconazole on cocaine self-administration in a rat model.
- To explore the potential role of corticosterone in mediating cocaine reinforcement.
- To assess ketoconazole as a potential adjunct therapy for cocaine abuse.
Main Methods:
- Adult male Wistar rats were trained to self-administer cocaine (0.125-0.5 mg/kg) or food during daily sessions.
- Rats were pretreated with ketoconazole (25 mg/kg, i.p.) or vehicle.
- Plasma corticosterone levels and self-administration behavior were measured.
Main Results:
- Ketoconazole significantly decreased plasma corticosterone levels.
- Ketoconazole reduced cocaine self-administration at lower doses (0.125-0.25 mg/kg) to levels seen during extinction.
- Cocaine self-administration at the highest dose (0.5 mg/kg) was not affected by ketoconazole.
- Food-reinforced responding remained unaffected by ketoconazole treatment.
Conclusions:
- Ketoconazole may serve as a potential therapeutic adjunct for cocaine abuse treatment.
- Corticosterone plays a significant role in cocaine reinforcement.
- Further research into ketoconazole and related compounds is warranted for addiction therapy.