Prolonged attenuation of the reinforcing strength of cocaine by chronic d-amphetamine in rhesus monkeys.
Prolonged attenuation of the reinforcing strength of cocaine by chronic d-amphetamine in rhesus monkeys.
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DOI：
10.1038/npp.2010.185
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发表时间：
2011-01
影响因子：
7.6
通讯作者：
Nader, Michael A.
中科院分区：
文献类型：
--
作者：
Czoty, Paul W.;Gould, Robert W.;Martelle, Jennifer L.;Nader, Michael A.
Chronic treatment with the indirect dopamine agonist d-amphetamine can reduce cocaine use in clinical trials and, in preclinical studies in laboratory animals, attenuates daily cocaine self-administration. The present study extended previous results to conditions designed to reflect a more clinically relevant experience of cocaine exposure and d-amphetamine treatment. Each morning, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR 50) schedule of reinforcement. After determining a dose-response curve for cocaine (0.005–0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule of reinforcement in the evening, cocaine self-administration sessions were suspended and d-amphetamine (0.01–0.056 mg/kg per hr, i.v.) was administered continuously for at least 24 days, except during cocaine self-administration sessions which were conducted using the PR schedule once every 8 days. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Cocaine- and food-maintained responding were also examined after discontinuation of d-amphetamine. Although individual differences in sensitivity were observed, d-amphetamine produced selective, qualitatively similar decreases in the reinforcing strength of cocaine in all monkeys that persisted at least 4 weeks. Moreover, cocaine dose-effect curves were shifted downward and/or to the right. For two weeks following discontinuation of d-amphetamine treatment, the reinforcing strength of cocaine varied within and across individuals however, on the whole no increased sensitivity was apparent. These data provide further support for the use of agonist medications for cocaine abuse, and extend the conditions under which such treatment is successful to those that incorporate clinically relevant patterns of cocaine use and drug treatment.
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DOI：
10.1124/jpet.106.107383
发表时间：
2007-02-01
影响因子：
3.5
作者：
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通讯作者：
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Negus, SS;Mello, NK
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作者：
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