Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules
Effect of baclofen on cocaine self-administration in rats reinforced under fixed-ratio 1 and progressive-ratio schedules
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DOI：
10.1007/s002130050056
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发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Roberts, DCS
中科院分区：
文献类型：
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作者：
Brebner, K;Phelan, R;Roberts, DCS
理由：最近的报告表明，γ-氨基丁酸（GABA）（B），激动剂巴氯芬减弱可卡因的强化作用。目的：进一步评估固定比例（FR）和渐进比例（PR）强化方案下巴氯芬对可卡因自我给药的影响。研究方法：在第一系列实验中，产生三个剂量-反应曲线，其检查三个剂量的巴氯芬（1.8、3.2或5.6mg/kg，i. p.）与在FR 1时间表下加强的四个单位注射剂量的可卡因（每次注射0.19、0.38、0.75和1.5 mg/kg）相比。为了比较，另一组大鼠用氟哌啶醇（32、56或100 μ g/kg，i.pl.单独的实验检查了巴氯芬（1.8、3.2或5.6mg/kg，i. p.）对同时可用的可卡因或食物强化的反应。结果：在FR 1时间表下，巴氯芬抑制低单位注射剂量可卡因的摄入，但不抑制高单位注射剂量可卡因的摄入。与氟哌啶醇相反，巴氯芬对注射间隔的分布没有影响，而是在可卡因自我给药中产生长时间的停顿。巴氯芬剂量依赖性地减少可卡因强化反应的PR时间表;同时获得食物强化的杠杆表明，动物保留的能力，以高利率的反应。结论：巴氯芬预处理对可卡因自我给药的影响取决于可卡因的单位注射剂量和时间表的反应要求。
Rationale: Recent reports have indicated that the gamma-aminobutyric acid (GABA)(B), agonist baclofen attenuates the reinforcing effects of cocaine. Objectives: To further evaluate the effect of baclofen on cocaine self-administration under a fixed ratio (FR) and progressive ratio (PR) schedule of reinforcement. Methods: In the first series of experiments, three dose-response curves were generated that examined the effect of three doses of baclofen (1.8, 3.2, or 5.6 mg/kg, i.p.) against four unit-injection doses of cocaine (0.19, 0.38, 0.75, and 1.5 mg/kg per injection) reinforced under a FR1 schedule. For comparison, an additional group of rats was pretreated with haloperidol (32, 56, or 100 mu g/kg, i.pli. A separate experiment examined the effect of baclofen (1.8, 3.2, or 5.6 mg/kg, i.p.) on responding for concurrently available cocaine or food reinforcement. Results: Under the FR1 schedule, baclofen suppressed intake of low but not high unit injection doses of cocaine. In contrast to haloperidol, baclofen had no effect on the distribution of inter-injection intervals and, instead, produced long pauses in cocaine self-administration. Baclofen dose dependently reduced cocaine-reinforced responding on a PR schedule; concurrent access to a food-reinforced lever demonstrated that the animals retained the capacity to respond at high rates. Conclusion: The effect of baclofen pretreatment on cocaine self-administration is dependent on the unit injection dose of cocaine and on the response requirements of the schedule.