Leo D, di Porzio U, Racagni G, Riva M A, Fumagalli F, Perrone-Capano C
Institute of Genetics and Biophysics A. Buzzati Traverso, CNR, Via Pietro Castellino, 111, 80131-Naples, Italy.
Exp Neurol. 2007 Feb;203(2):472-80. doi: 10.1016/j.expneurol.2006.08.024. Epub 2006 Oct 27.
Chronic cocaine use leads to pronounced alterations in neuronal functions in brain circuits associated with reward. In the present study, we examined in the rat midbrain the effects of acute, subchronic (5 days) and chronic cocaine treatments (14 days) on the gene expression of transcription factors involved in the development and maintenance of dopaminergic neurons. We show that chronic, but not acute or subchronic, cocaine administration downregulates Nurr1 and Pitx3 transcripts whereas En1 transcripts are upregulated. Conversely, Lmx1b and En2 transcripts are not affected by the drug treatment, indicating that the modulation of the midbrain transcription factors analyzed is highly selective. Interestingly, modification of the gene expression for these transcription factors persists in midbrain as long as two weeks after the last drug administration, suggesting that it may account for some of the enduring alterations in midbrain dopaminergic circuits associated with chronic cocaine use.
长期使用可卡因会导致与奖赏相关的脑回路中神经元功能发生显著改变。在本研究中，我们在大鼠中脑检测了急性、亚慢性（5天）和慢性可卡因处理（14天）对参与多巴胺能神经元发育和维持的转录因子基因表达的影响。我们发现，长期而非急性或亚慢性可卡因给药会下调Nurr1和Pitx3转录本，而En1转录本上调。相反，Lmx1b和En2转录本不受药物处理影响，这表明所分析的中脑转录因子的调节具有高度选择性。有趣的是，这些转录因子的基因表达改变在末次给药后长达两周的时间里仍持续存在于中脑，这表明它可能是与长期使用可卡因相关的中脑多巴胺能回路某些持久改变的原因。
