Institute for Neuroscience, The University of Texas at Austin, Austin, Texas 78712, USA.
Synapse. 2011 Apr;65(4):309-20. doi: 10.1002/syn.20849. Epub 2010 Oct 11.
The critical brain areas and molecular mechanisms involved in drug abuse and dependence have been extensively studied. Drug-induced persistent behaviors such as sensitization, tolerance, or relapse, however, far outlast any previously reported mechanisms. A challenge in the field of addiction, therefore, has been to identify drug-induced changes in brain circuitry that may subserve long-lasting changes in behavior. This study examined behavioral changes and electron microscopic evidence of altered synaptic connectivity within the nucleus accumbens (NAc) following repeated administration of cocaine or morphine. The unbiased quantitative stereological physical disector method was used to estimate the number of synapses per neuron. Increases in the synapse-to-neuron ratio were found in the NAc shell of cocaine-treated (49.1%) and morphine-treated (55.1%) rats and in the NAc core of cocaine-treated animals (49.1%). This study provides direct ultrastructural evidence of drug-induced synaptic plasticity and identifies synaptic remodeling as a potential neural substrate underlying drug-induced behavioral sensitization.
该研究通过使用无偏定量立体学物理剖分方法来估计每个神经元的突触数量，检测了重复给予可卡因或吗啡后，伏隔核（NAc）内行为变化和突触连接改变的电镜证据。结果发现，可卡因处理组（49.1%）和吗啡处理组（55.1%）大鼠的 NAc 壳以及可卡因处理组（49.1%）大鼠的 NAc 核内突触/神经元比值增加。该研究提供了药物诱导突触可塑性的直接超微结构证据，并将突触重塑确定为药物诱导行为敏化的潜在神经基础。
