Basheer R, Tempel A
Department of Psychiatry, Hillside Hospital, Long Island Jewish Medical Center, Albert Einstein College of Medicine, Glen Oaks, New York 11004.
J Neurosci Res. 1993 Dec 1;36(5):551-7. doi: 10.1002/jnr.490360507.
The mechanisms involved in the development of morphine tolerance and dependence are still unknown. Recently much attention has been directed toward the changes in post receptor events. Opiate receptors, like other hormone and neurotransmitter receptors, have been shown to mediate their effects through guanine nucleotide binding proteins (G-proteins). This, in turn, may cause alterations in intracellular events, one of which is transcription of specific genes. We investigated the changes in the levels of mRNA of proenkephalin (PPE) and prodynorphin (DYN) and the stimulatory G protein alpha subunit (G alpha s) in adult morphine tolerant rats. Chronic morphine treatment induced reciprocal alterations in the levels of opioid peptide mRNA and G alpha s mRNA in discrete brain regions. In striatum, PPE mRNA decreased by 49% (P < .01) and in hypothalamus, DYN mRNA showed a decrease of 21% (P < .01). In contrast, G alpha s mRNA increased 20% (P < .01) in striatum and 97% (P < .01), in hypothalamus. In hippocampus the changes were reversed: PPE mRNA increased (55%, P < .05) and G alpha s mRNA decreased (33%, P < .01). Frontal cortex exhibited a small decrease in PPE (11.5%, P < .05) without any change on G alpha s or DYN mRNA levels. These reciprocal alterations suggest an opposing mode of regulation of G alpha s and PPE/DYN gene expression in morphine tolerant animals.
吗啡耐受性和依赖性产生的机制仍不清楚。最近，很多注意力都集中在受体后事件的变化上。阿片受体与其他激素和神经递质受体一样，已被证明通过鸟嘌呤核苷酸结合蛋白（G蛋白）介导其作用。这进而可能导致细胞内事件的改变，其中之一是特定基因的转录。我们研究了成年吗啡耐受大鼠中前脑啡肽（PPE）、前强啡肽（DYN）的mRNA水平以及刺激性G蛋白α亚基（Gαs）的变化。慢性吗啡处理诱导离散脑区中阿片肽mRNA水平和Gαs mRNA水平发生相反的变化。在纹状体中，PPE mRNA下降了49%（P < 0.01），在下丘脑中，DYN mRNA下降了21%（P < 0.01）。相反，纹状体中Gαs mRNA增加了20%（P < 0.01），下丘脑中增加了97%（P < 0.01）。在海马体中，变化则相反：PPE mRNA增加（55%，P < 0.05），Gαs mRNA下降（33%，P < 0.01）。额叶皮质中PPE略有下降（11.5%，P < 0.05），而Gαs或DYN mRNA水平没有任何变化。这些相反的变化表明在吗啡耐受动物中Gαs和PPE/DYN基因表达存在相反的调节模式。
