Increased breakpoints on a progressive ratio schedule reinforced by IV cocaine are associated with reduced locomotor activation and reduced dopamine efflux in nucleus accumbens shell in rats
Increased breakpoints on a progressive ratio schedule reinforced by IV cocaine are associated with reduced locomotor activation and reduced dopamine efflux in nucleus accumbens shell in rats
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DOI：
10.1007/s00213-007-0919-4
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Roberts, David C. S.
中科院分区：
文献类型：
--
作者：
Lack, Christopher M.;Jones, Sara R.;Roberts, David C. S.
理论基础有人假设中脑边缘多巴胺（DA）系统内神经化学效应的敏化可能是成瘾过程的特定方面。我们最近开发了一种自我管理的程序，它产生增加的反应，可卡因加强了累进比率（PR）的时间表。这可能反映了增加的动机，自我管理可卡因，一个标志addiction.Objectives本实验的目标是调查行为和神经化学变化与增加可卡因自我管理PR schedule.Materials和方法大鼠自我管理可卡因超过14天的PR时间表下。可卡因刺激的自发活动进行了评价之前，以及1或14天后自我管理的培训。可卡因引起的DA的变化，在相同的动物的核心和壳的核cubens也examined.Results科目显示随着时间的推移，增加响应，约200%的基线。可卡因诱导的自发活动减少，在两个撤药时间相比，幼稚的动物。微透析显示，在两个时间点，自我给药后，丘脑核核心多巴胺反应无差异。然而，有一个显着的下降，在多巴胺的反应可卡因的壳的nucleus abens.Conclusion目前的结果表明，一个渐进的增加断点上的PR时间表可以建立在大鼠的时候，可卡因的能力，增加细胞外DA水平和刺激自发活动减少。因此，中脑边缘DA系统的敏化不能解释观察到的服药行为的变化。
Rationale It has been hypothesized that sensitization of the neurochemical effects within the mesolimbic dopamine (DA) system might account for specific aspects of the addiction process. We have recently developed a self-administration procedure which produces increases in responding reinforced by cocaine on a progressive ratio (PR) schedule. This may reflect an increased motivation to self-administer cocaine, one hallmark of addiction.Objectives The goal of this experiment was to investigate behavioral and neurochemical changes associated with increased cocaine self-administration on a PR schedule.Materials and methods Rats self-administered cocaine over 14 days under a PR schedule. Cocaine-stimulated locomotor activity was evaluated before as well as 1 or 14 days after self-administration training. Cocaine-induced DA changes in the core and shell of the nucleus accumbens in the same animals were also examined.Results Subjects showed increased responding over time, to about 200% of baseline. Cocaine-induced locomotor activation was decreased at both withdrawal times compared to naive animals. Microdialysis showed no differences after self-administration in the nucleus accumbens core dopamine response at either time point. There was, however, a significant decrease in the dopamine response to cocaine in the shell of the nucleus accumbens.Conclusion The present results demonstrate that a progressive increase in breakpoints on a PR schedule can be established in rats at a time when the ability of cocaine to increase extracellular DA levels and stimulate locomotor activity is reduced. Therefore, sensitization of the mesolimbic DA system does not account for the observed change in drug-taking behavior.