Dawirs R R, Teuchert-Noodt G, Nossoll M
Department of Neuroanatomy, Faculty of Biology, University of Bielefeld, Germany.
Eur J Pharmacol. 1997 May 30;327(2-3):117-23. doi: 10.1016/s0014-2999(97)89650-1.
Using a selective antibody serum against glutaraldehyde-conjugated gamma-aminobutyric acid (GABA), GABAergic neurons were identified in the medial prefrontal cortex of young adult gerbils (Meriones unguiculatus) following a single non-invasive dose of methamphetamine (25 mg/kg i.p.) applied at the age of 90 days. GABA-immunoreactive profiles were electron microscopically counted in a defined test field (0.875 mm2) covering the prefrontal prelimbic area after a single dose of either methamphetamine or saline. Within 30 days following the drug challenge the density of GABAergic innervation significantly increased by about 20%. Several lines of previous investigation indicate that a single dose of methamphetamine is an appropriate stimulus to cause selective autotoxic destruction of certain prefrontal dopamine fibres due to drug-induced hyperactivation. There is further indication of postsynaptic and transneuronal neuroplasticity since the densities of dendritic spines on prefrontal pyramidal cells went through a significant sequence of post-drug gain and loss. These structural dynamics resemble typical alterations seen after classical mechanical or chemical lesioning in other regions of the brain. The present results on drug-induced reactive neuroplasticity are discussed together with the current understanding of stimulus-induced adaptive reorganization in the mammalian central nervous system.
使用针对戊二醛结合的γ-氨基丁酸（GABA）的选择性抗体血清，在90日龄的幼年成年沙鼠（长爪沙鼠）单次非侵入性给予甲基苯丙胺（25mg/kg腹腔注射）后，在内侧前额叶皮质中鉴定出GABA能神经元。在单次给予甲基苯丙胺或生理盐水后，在覆盖前额叶前边缘区的特定测试区域（0.875平方毫米）中通过电子显微镜对GABA免疫反应性轮廓进行计数。在药物激发后的30天内，GABA能神经支配密度显著增加了约20%。先前的几项研究表明，单次剂量的甲基苯丙胺是一种合适的刺激，可导致某些前额叶多巴胺纤维因药物诱导的过度激活而发生选择性自毒性破坏。进一步有证据表明存在突触后和跨神经元神经可塑性，因为前额叶锥体细胞上树突棘的密度经历了药物后显著的增加和减少过程。这些结构动态类似于在大脑其他区域经典机械或化学损伤后所见的典型变化。本文关于药物诱导的反应性神经可塑性的结果与目前对哺乳动物中枢神经系统中刺激诱导的适应性重组的理解一起进行了讨论。
