Brady Anne Marie, Glick Stanley D, O'Donnell Patricio
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.
J Neurosci. 2005 Jul 13;25(28):6687-95. doi: 10.1523/JNEUROSCI.0643-05.2005.
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.
精神兴奋剂诱导的大鼠运动活动行为敏化已被提出作为成瘾模型，且伴有伏隔核及相关神经回路的神经适应性变化。在此，我们采用体内细胞内记录法，研究了反复给予甲基苯丙胺（5.0毫克/千克；5天）后出现或未出现行为敏化的动物伏隔核神经元的电生理特性。尽管伏隔核神经元的自发活动基本未变，但在敏化动物中，控制膜电位状态的多种突触相互作用受到了破坏。例如，在未敏化和生理盐水处理的动物中，刺激腹侧被盖区会减弱伏隔核对前额叶皮层激活的反应，但在敏化动物中则不然。急性给予甲基苯丙胺（0.5毫克/千克）会消除未敏化和生理盐水处理动物伏隔核的兴奋和抑制状态，这表明该区域正常信息处理受到了破坏。然而，急性给予甲基苯丙胺未能影响敏化动物伏隔核神经元的这种模式。这些结果表明，急性和反复给予甲基苯丙胺均可破坏伏隔核中的突触相互作用；然而，这些改变的性质关键取决于行为敏化的程度。据推测，未敏化和生理盐水处理动物对急性甲基苯丙胺的反应可能具有功能适应性，而在敏化动物中观察到的神经适应性变化可能是适应不良的，且对伏隔核信息处理有害。
