Attenuation of d-amphetamine self-administration by baclofen in the rat:: behavioral and neurochemical correlates
Attenuation of d-amphetamine self-administration by baclofen in the rat:: behavioral and neurochemical correlates
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DOI：
10.1007/s00213-004-1968-6
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发表时间：
2005-02-01
影响因子：
3.4
通讯作者：
Phillips, AG
中科院分区：
文献类型：
--
作者：
Brebner, K;Ahn, S;Phillips, AG
理由：最近的报告表明，γ-氨基丁酸（GABA）能化合物减弱可卡因在大鼠中的强化作用。巴氯芬是一种GABA（B）受体激动剂，在这方面似乎特别有效，表明GABA（B）受体活化在介导抗可卡因作用中至关重要。安非他明和可卡因一样，是一种精神兴奋剂，在人类中有很高的滥用潜力。目的：本研究的目的是确定巴氯芬是否可以减弱d-苯丙胺（dAMPH）在大鼠中的增强作用。生成剂量-反应曲线以检查三种剂量的巴氯芬（1.8、3.2或5.6mg/kg，IP）对dAMPH静脉内自我给药（IVSA）的影响。训练不同的组在固定比例（FR）或渐进比例（PR）强化方案下自我施用两个剂量的dAMPH（每次注射0.1 mg/kg或0.2 mg/kg）。在另一组大鼠中进行微透析，以检查巴氯芬对dAMPH诱导的多巴胺（DA）流出增加的影响。结果如下：巴氯芬预处理产生剂量依赖性减少dAMPH反应的FR和PR的时间表下，衰减dAMPH诱导的DA水平的增加NAc。总结：这些结果增加了以前的研究结果表明，巴氯芬减弱精神兴奋剂药物的强化作用，并建议进一步调查GABA（B）受体激动剂对药物自我管理的影响是必要的。
Rationale: Recent reports have demonstrated that gamma-aminobutyric acid (GABA)-ergic compounds attenuate the reinforcing effects of cocaine in rats. Baclofen, a GABA(B) receptor agonist, appears to be particularly effective in this respect, suggesting that GABA(B) receptor activation is critically involved in mediating anti-cocaine effects. Amphetamine, like cocaine, is a psychomotor stimulant with high abuse potential in humans. Objectives: The purpose of the present investigation was to determine whether baclofen may attenuate the reinforcing effects of d-amphetamine (dAMPH) in rats. Dose-response curves were generated to examine the effect of three doses of baclofen (1.8, 3.2 or 5.6 mg/kg, IP) on dAMPH intravenous self-administration (IVSA). Separate groups were trained to self-administer two doses of dAMPH (0.1 mg/kg or 0.2 mg/kg per injection) under either a fixed-ratio (FR) or progressive ratio (PR) schedule of reinforcement. Microdialysis was performed in an additional group of rats to examine the effect of baclofen on dAMPH-induced increases in dopamine (DA) efflux in the nucleus accumbens (NAc). Results: Pretreatment with baclofen produced dose-dependent reductions in responding for dAMPH under both the FR and PR schedules, and attenuated dAMPH-induced increases in DA levels in the NAc. Conclusion: These results add to previous findings showing that baclofen attenuates the reinforcing effects of psychostimulant drugs, and suggest that further investigation into the effects of GABA(B) receptor agonists on drug self-administration is warranted.