慢性甲基苯丙胺导致大鼠伏隔核和中脑即刻早期基因的差异表达。
Chronic Methamphetamine Causes Differential Expression of Immediate Early Genes in the Nucleus Accumbens and Midbrain of Rats.
作者信息
Garrett Tiffany, Tulloch Ingrid, McCoy Michael T, Ladenheim Bruce, Jayanthi Subramaniam, Krasnova Irina, Beauvais Genevieve, Hodges Amber, Davis Carolyn, Cadet Jean Lud
机构信息
Molecular Neuropsychiatry Branch, DHHS/NIH/NIDA-Intramural Research Program, 251 Bayview Blvd, Baltimore, MD 21224, USA.
出版信息
J Drug Alcohol Res. 2012;1(1). doi: 10.4303/jdar/235626.
The present study investigated whether chronic methamphetamine (METH) would suppress METH-induced mRNA expression of immediate early genes (IEGs) in the rat brain. Rats were given METH or saline over two weeks. After an overnight withdrawal, saline- and METH-pretreated rats received an acute saline or METH challenge. The acute METH challenge increased expression of members of activator protein 1 (AP-1) and Nr4a IEG families in the nucleus accumbens (NAc) and midbrain of saline-pretreated rats. Chronic METH exposure attenuated the effects of acute METH challenge on AP-1 IEG expression in the NAc. However, chronic METH failed to attenuate acute METH-induced increases of Nr4a1 and Nr4a3 expression in the NAc. In contrast to observations in the NAc, chronic METH did not prevent acute METH-induced changes in IEG expression in the midbrain. These results suggest that these two brain regions that are implicated in neuroplastic effects of illicit substances might be differentially affected by psychostimulants.
本研究调查了长期使用甲基苯丙胺（METH）是否会抑制大鼠脑中METH诱导的即刻早期基因（IEGs）的mRNA表达。大鼠在两周内给予METH或生理盐水。经过一夜的戒断后，给予生理盐水和METH预处理的大鼠进行急性生理盐水或METH激发试验。急性METH激发试验增加了给予生理盐水预处理大鼠伏隔核（NAc）和中脑中活化蛋白1（AP-1）和Nr4a IEG家族成员的表达。长期暴露于METH减弱了急性METH激发试验对NAc中AP-1 IEG表达的影响。然而，长期使用METH未能减弱急性METH诱导的NAc中Nr4a1和Nr4a3表达的增加。与在NAc中的观察结果相反，长期使用METH并不能阻止急性METH诱导的中脑IEG表达的变化。这些结果表明，这两个与非法物质神经可塑性效应有关的脑区可能受到精神兴奋剂的不同影响。
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