Heng Li-Jun, Yang Jing, Liu Yi-Hui, Wang Wen-Ting, Hu San-Jue, Gao Guo-Dong
Institute of Neuroscience, Fourth Military Medical University, Xi'an, Shaanxi 710032, People's Republic of China.
Synapse. 2008 Oct;62(10):775-82. doi: 10.1002/syn.20551.
It is well known that the nucleus accumbens plays an important role in drug reinforcing effect and relapse. However, the cellular neuroadaptations that take place in accumbens neurons after repeated drug exposure are still not well understood, especially for opioids. Here, we examined how nucleus accumbens neuronal excitability becomes affected in rats exposed to morphine using whole-cell patch-clamp recordings. Medium spiny neurons recorded from brain slices of repeated morphine treated rats exhibited a significant decrease in the intrinsic excitability after 3-4 days withdrawal, compared to that of neurons from saline treated animals, which was indicated by the increase of current to evoke the first spike and the decrease of spike number induced by depolarizing current steps in the morphine group. Moreover, the excitability decrease was accompanied by related membrane property changes, such as resting membrane potential hyperpolarization, input resistance, and membrane time constant decrease, inward rectification increase, and action potential duration decrease. Taken together, repeated morphine exposure and short-term withdrawal may reduce nucleus accumbens activity and output by modulating intrinsic membrane properties of its output neurons, which could be an important neuroadaptation process that mediates morphine addictive effect.
众所周知，伏隔核在药物强化作用和复吸中起着重要作用。然而，反复接触药物后伏隔核神经元发生的细胞神经适应性变化仍未得到充分了解，尤其是对于阿片类药物而言。在此，我们使用全细胞膜片钳记录技术研究了暴露于吗啡的大鼠中伏隔核神经元兴奋性是如何受到影响的。与盐水处理动物的神经元相比，从反复接受吗啡处理的大鼠脑片中记录到的中等棘状神经元在戒断3 - 4天后表现出固有兴奋性显著降低，这在吗啡组中表现为诱发第一个动作电位的电流增加以及去极化电流刺激诱发的动作电位数量减少。此外，兴奋性降低伴随着相关膜特性的变化，如静息膜电位超极化、输入电阻和膜时间常数减小、内向整流增加以及动作电位时程缩短。综上所述，反复接触吗啡和短期戒断可能通过调节其输出神经元的固有膜特性来降低伏隔核的活性和输出，这可能是介导吗啡成瘾作用的一个重要神经适应性过程。
