Michelhaugh S K, Pimputkar G, Gnegy M E
Department of Pharmacology, 2220E MSRBIII, University of Michigan Medical School, Ann Arbor, MI 48109-0634, USA.
Brain Res Mol Brain Res. 1998 Nov 12;62(1):35-42. doi: 10.1016/s0169-328x(98)00233-2.
To assess whether calmodulin (CaM) gene expression could have a role in behavioral sensitization induced by repeated, intermittent amphetamine, CaM protein and mRNA of the three separate CaM genes were measured in several different brain areas from rats repeatedly administered saline or amphetamine. Rats were injected twice weekly for five weeks, followed by one week of withdrawal. CaM protein and mRNA were measured in dorsal striatum, limbic forebrain, prefrontal cortex, ventral mesencephalon and piriform cortex. There were increases of CaM protein content and decreases of CaM I mRNA in the dorsal striatum and prefrontal cortex. CaM II mRNA was also decreased in the dorsal striatum. A decrease of CaM protein and an increase of CaM I mRNA were found in the ventral mesencephalon. There was no change of CaM protein in the limbic forebrain, although a decrease of CaM I mRNA was detected. CaM protein and mRNA were not altered in the piriform cortex. Our findings demonstrate that both CaM content and mRNA are altered after an amphetamine regimen leading to sensitization. The fact that the changes in CaM content and mRNA are in dopaminergic brain areas associated with sensitization suggests that CaM could contribute to neurochemical events underlying behavioral sensitization to amphetamine.
为评估钙调蛋白（CaM）基因表达是否在反复间歇性给予苯丙胺所诱导的行为敏化中发挥作用，我们检测了反复给予生理盐水或苯丙胺的大鼠几个不同脑区中三种不同CaM基因的CaM蛋白和mRNA水平。大鼠每周注射两次，持续五周，随后停药一周。我们检测了背侧纹状体、边缘前脑、前额叶皮质、腹侧中脑和梨状皮质中的CaM蛋白和mRNA。背侧纹状体和前额叶皮质中CaM蛋白含量增加，CaM I mRNA减少。背侧纹状体中CaM II mRNA也减少。腹侧中脑中发现CaM蛋白减少，CaM I mRNA增加。边缘前脑中CaM蛋白没有变化，尽管检测到CaM I mRNA减少。梨状皮质中CaM蛋白和mRNA没有改变。我们的研究结果表明，在导致敏化的苯丙胺给药方案后，CaM含量和mRNA均发生了改变。CaM含量和mRNA的变化发生在与敏化相关的多巴胺能脑区，这一事实表明CaM可能参与了对苯丙胺行为敏化的神经化学事件。
