Division of Endocrinology, Department of Medicine, Charles Drew University of Medicine and Sciences-UCLA School of Medicine, Los Angeles, CA 90059, USA.
Neuroscience. 2010 May 5;167(2):554-66. doi: 10.1016/j.neuroscience.2010.01.043. Epub 2010 Feb 6.
Addictive drugs including opioids activate signal transduction pathways that regulate gene expression in the brain. However, changes in CNS gene expression following morphine exposure are poorly understood. We determined changes in gene expression following short- and long-term morphine treatment in the hypothalamus and pituitary using genome-wide DNA microarray analysis and confirmed those alterations in gene expression by real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In the hypothalamus, short-term morphine administration up-regulated (at least twofold) 39 genes and down-regulated six genes. Long-term morphine treatment up-regulated 35 genes and down-regulated 51 genes. In the pituitary, short-term morphine administration up-regulated 110 genes and down-regulated 29 genes. Long-term morphine treatment up-regulated 85 genes and down-regulated 37 pituitary genes. Microarray analysis uncovered several genes involved in food intake (neuropeptide Y, agouti-related protein, and cocaine and amphetamine-regulated transcript) whose expression was strongly altered by morphine exposure in either the hypothalamus or pituitary. Subsequent RT-PCR analysis confirmed similar regulation in expression of these genes in the hypothalamus and pituitary. Finally, we found functional correlation between morphine-induced alterations in food intake and regulation of genes involved in this process. Changes in genes related to food intake may uncover new pathways related to some of the physiological effects of opioids.
成瘾性药物，包括阿片类药物，会激活调节大脑基因表达的信号转导通路。然而，吗啡暴露后中枢神经系统基因表达的变化还知之甚少。我们使用全基因组 DNA 微阵列分析确定了短时间和长时间吗啡处理后下丘脑和垂体中基因表达的变化，并通过实时逆转录聚合酶链反应（RT-PCR）分析证实了这些基因表达的改变。在下丘脑，短期吗啡给药上调（至少两倍）39 个基因，下调 6 个基因。长期吗啡处理上调 35 个基因，下调 51 个基因。在垂体中，短期吗啡给药上调 110 个基因，下调 29 个基因。长期吗啡处理上调 85 个基因，下调 37 个垂体基因。微阵列分析揭示了一些参与食物摄入的基因（神经肽 Y、肥胖相关蛋白和可卡因和安非他命调节转录物），它们的表达在无论是在下丘脑还是垂体中都受到吗啡暴露的强烈影响。随后的 RT-PCR 分析证实了这些基因在下丘脑和垂体中的表达也有类似的调节。最后，我们发现了吗啡诱导的食物摄入变化与参与该过程的基因调节之间的功能相关性。与食物摄入相关的基因变化可能揭示与阿片类药物某些生理作用相关的新途径。
