Cerruti C, Pilotte N S, Uhl G, Kuhar M J
NIH, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Brain Res Mol Brain Res. 1994 Mar;22(1-4):132-8. doi: 10.1016/0169-328x(94)90040-x.
Male, Lewis rats were treated intravenously for 2 weeks with saline or cocaine using a dose and injection schedule that is similar to the doses and patterns of cocaine intake in self-administration studies. Ten days after cessation of treatment, dopamine transporter binding levels were decreased in the nucleus accumbens but not in the striatum. In situ hybridization studies revealed decreases in dopamine transporter mRNA that were restricted to cells of the interfascicular and caudal linear nuclei; these dopaminergic cell groups, found in the ventral tegmentum, project to the nucleus accumbens and other limbic areas. Other dopaminergic cell groups in midbrain which project mainly to other areas did not show a decrease in mRNA. These results indicate that gene expression can be altered many days after withdrawal from cocaine, and provide an example of transporter regulation by a change in gene expression.
雄性Lewis大鼠按照与自我给药研究中可卡因摄入剂量和模式相似的剂量和注射方案，静脉注射生理盐水或可卡因，持续2周。治疗停止10天后，伏隔核中的多巴胺转运体结合水平降低，但纹状体中未降低。原位杂交研究显示，多巴胺转运体mRNA的减少仅限于束间核和尾侧线性核的细胞；这些多巴胺能细胞群位于腹侧被盖区，投射到伏隔核和其他边缘区域。中脑中主要投射到其他区域的其他多巴胺能细胞群的mRNA没有减少。这些结果表明，从可卡因戒断许多天后基因表达可能会发生改变，并提供了一个通过基因表达变化来调节转运体的例子。
