Selective disruption of nucleus accumbens gating mechanisms in rats behaviorally sensitized to methamphetamine
Selective disruption of nucleus accumbens gating mechanisms in rats behaviorally sensitized to methamphetamine
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DOI：
10.1523/jneurosci.0643-05.2005
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发表时间：
2005-07-13
影响因子：
5.3
通讯作者：
O'Donnell, P
中科院分区：
文献类型：
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作者：
Brady, AM;Glick, SD;O'Donnell, P
大鼠中精神兴奋剂诱导的自发活动的行为敏化已被提出作为成瘾模型，并伴随着丘脑核和相关回路中的神经适应。在这里，我们使用在体内细胞内记录，以检查电生理特性的动物，没有或没有表现出行为致敏后，重复甲基苯丙胺（5.0毫克/公斤; 5天）的神经元。虽然自发活动的神经元几乎没有变化，控制膜电位状态的多个突触相互作用被破坏致敏动物。例如，刺激腹侧被盖区会减弱非致敏动物和生理盐水处理动物对前额叶皮层激活的反应，但在致敏动物中则不然。急性甲基苯丙胺（0.5毫克/公斤）取消了在nonsensitized和盐水处理的动物，表明在这方面的正常信息处理的中断的阿托本斯向上和向下状态。然而，急性甲基苯丙胺未能影响这种模式在致敏动物的神经元。这些结果表明，急性和重复的甲基苯丙胺管理可以破坏突触的相互作用，在神经核，然而，这些改变的性质严重依赖于行为敏化的程度。据推测，在非致敏和盐水处理的动物急性甲基苯丙胺的反应可能是功能适应，而在致敏动物中观察到的神经适应可能是适应不良和有害的信息处理。
Behavioral sensitization of psychostimulant-induced locomotor activity in rats has been proposed as a model of addiction and is accompanied by neuroadaptations in the nucleus accumbens and related circuits. Here, we used in vivo intracellular recordings to examine electrophysiological properties of accumbens neurons from animals that did or did not exhibit behavioral sensitization after repeated methamphetamine (5.0 mg/kg; 5 d). Although spontaneous activity of accumbens neurons was virtually unchanged, multiple synaptic interactions controlling membrane potential states were disrupted in sensitized animals. For example, stimulation of the ventral tegmental area attenuated accumbens responses to prefrontal cortex activation in nonsensitized and saline-treated animals, but not in sensitized animals. Acute methamphetamine (0.5 mg/kg) abolished accumbens up and down states in nonsensitized and saline-treated animals, suggesting a disruption of normal information processing in this area. However, acute methamphetamine failed to affect this pattern in accumbens neurons from sensitized animals. These results suggest that both acute and repeated methamphetamine administration can disrupt synaptic interactions in the nucleus accumbens; however, the nature of these alterations depends critically on the extent of behavioral sensitization. It is speculated that the response to acute methamphetamine in nonsensitized and saline-treated animals may be functionally adaptive, whereas the neuroadaptations observed in sensitized animals may be maladaptive and detrimental to accumbens information processing.