Isola Raffaella, Zhang Hailing, Duchemin Anne-Marie, Tejwani Gopi A, Neff Norton H, Hadjiconstantinou Maria
Department of Psychiatry, The Ohio State University School of Medicine and Public Health, 5034 Graves Hall, 333 West 10th Avenue, Columbus, OH 43210, USA.
Neurosci Lett. 2002 May 31;325(1):67-71. doi: 10.1016/s0304-3940(02)00240-9.
We studied the changes of met-enkephalin (Met-Enk) content and preproenkephalin (PPE) mRNA in the striatum in a mouse model of nicotine abstinence. Nicotine, 2 mg/kg, s.c., was administered four times daily for 14 days and Met-Enk and PPE mRNA evaluated at various times (4-96 h) following drug discontinuation. Met-Enk, assayed by radioimmunoassay, was increased in the ventral (nucleus accumbens) but not dorsal (putamen/caudate) striatum, while PPE mRNA, assayed in whole striatum by Northern blotting was elevated. Both changes were seen early during withdrawal and lasted over 72 h. In situ hybridization revealed enhanced signal in the dorsal striatum, mostly laterally, and smaller increases in the rostral pole, core and shell of the nucleus accumbens. These observations indicate that during nicotine withdrawal, striatal enkephalinergic neurons undergo adaptative responses, which might contribute to the abstinence behavioral syndrome.
我们在尼古丁戒断小鼠模型中研究了纹状体中甲硫氨酸脑啡肽（Met-Enk）含量和前脑啡肽原（PPE）mRNA的变化。皮下注射2mg/kg尼古丁，每日4次，持续14天，并在停药后的不同时间点（4 - 96小时）评估Met-Enk和PPE mRNA。通过放射免疫分析法测定，腹侧（伏隔核）纹状体中的Met-Enk增加，而背侧（壳核/尾状核）纹状体中未增加，同时通过Northern印迹法在整个纹状体中测定的PPE mRNA升高。这两种变化在戒断早期出现，并持续超过72小时。原位杂交显示背侧纹状体信号增强，主要在外侧，伏隔核的喙极、核心和壳核也有较小程度的增加。这些观察结果表明，在尼古丁戒断期间，纹状体脑啡肽能神经元会发生适应性反应，这可能导致戒断行为综合征。
