Effects of the combination of metyrapone and oxazepam on intravenous nicotine self-administration in rats

甲吡酮与奥沙西泮合用对大鼠静脉注射尼古丁自我给药的影响

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作者:Nicholas E Goeders, Ami Cohen, Barbara S Fox, Marc R Azar, Olivier George, George F Koob

Conclusions

The results of this study suggest a potential utility of the combination of metyrapone and oxazepam for smoking cessation in humans.

Methods

Several dose combinations of metyrapone (12.5, 25 or 50 mg/kg) and oxazepam (5 or 10 mg/kg) were tested in rats trained to intravenously (IV) self-administer nicotine (0.03 mg/kg/infusion) during 1-h self-administration sessions using both fixed-ratio and progressive-ratio (PR) schedules of reinforcement.

Results

The administration of low doses of metyrapone and oxazepam in combination significantly decreased IV nicotine self-administration in rats. At the lowest doses of 12.5 mg/kg of metyrapone and 5 mg/kg of oxazepam, the drugs alone did not decrease IV nicotine self-administration, but the combination was effective. Varenicline was also tested using the fixed-ratio schedule, and reductions in nicotine intake were similar to those seen with the moderate dose of the combination. Conclusions: The results of this study suggest a potential utility of the combination of metyrapone and oxazepam for smoking cessation in humans.

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