Gudehithlu K P, Bhargava H N
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Health Sciences Center 60612, USA.
Peptides. 1995;16(3):415-9. doi: 10.1016/0196-9781(94)00199-g.
The effect of morphine tolerance/dependence and abstinence on the preproenkephalin (PPE) gene expression was determined in brain regions and spinal cord of the rat. Male Sprague-Dawley rats were rendered tolerant and physically dependent on morphine by SC implantation of six pellets, each containing 75 mg of morphine base, during a 7-day period. Placebo pellet-implanted rats served as controls. In tolerant rats, the pellets were left in place at the time of sacrifice whereas in abstinent rats, the pellets were removed 16 h prior to sacrificing. The levels of PPE mRNA were determined in brain regions (striatum, cortex, pons-medulla, hypothalamus, amygdala, and midbrain) and spinal cord. The levels of PPE mRNA increased significantly in the cortex (62%) and the spinal cord (352%) of morphine-tolerant rats when compared to placebo pellet-implanted control rats. In other brain regions, the levels of PPE mRNA in placebo and morphine-tolerant rats did not differ. On the other hand, in morphine-abstinent rats, the levels of PPE mRNA increased in the striatum (62%) and hypothalamus (34%) but were decreased in pons-medulla (68%), midbrain (51%), and spinal cord (36%) in comparison to the placebo controls. The results clearly demonstrate differential changes in enkephalin gene expression in brain regions and spinal cord of the abstinent and nonabstinent morphine-tolerant/dependent rats.
在大鼠的脑区和脊髓中测定了吗啡耐受/依赖及戒断对前脑啡肽原（PPE）基因表达的影响。雄性斯普拉格-道利大鼠在7天内通过皮下植入6粒每粒含75 mg吗啡碱的药丸而产生吗啡耐受性和身体依赖性。植入安慰剂药丸的大鼠作为对照。对于耐受大鼠，在处死时药丸留在原位，而对于戒断大鼠，在处死前16小时取出药丸。在前脑啡肽原mRNA水平在脑区（纹状体、皮层、脑桥-延髓、下丘脑、杏仁核和中脑）和脊髓中进行测定。与植入安慰剂药丸的对照大鼠相比，吗啡耐受大鼠的皮层（62%）和脊髓（352%）中的前脑啡肽原mRNA水平显著升高。在其他脑区，安慰剂组和吗啡耐受大鼠的前脑啡肽原mRNA水平没有差异。另一方面，与安慰剂对照相比，吗啡戒断大鼠的纹状体（62%）和下丘脑（34%）中的前脑啡肽原mRNA水平升高，但脑桥-延髓（68%）、中脑（51%）和脊髓（36%）中的前脑啡肽原mRNA水平降低。结果清楚地表明了戒断和未戒断的吗啡耐受/依赖大鼠的脑区和脊髓中脑啡肽基因表达的差异变化。
