Di Benedetto M, D'addario C, Candeletti S, Romualdi P
Department of Pharmacology, University of Bologna, Irnerio 48, 40126 Bologna, Italy.
Neuroscience. 2006;137(1):187-96. doi: 10.1016/j.neuroscience.2005.09.015. Epub 2005 Nov 10.
The prodynorphin system is implicated in the neurochemical mechanism of psychostimulants. Exposure to different drugs of abuse can induce neuroadaptations in the brain and affect opioid gene expression. The present study aims to examine the possibility of a common neurobiological substrate in drug addiction processes. We studied the effects of single and repeated 3,4-methylenedioxy-N-methylamphetamine ('Ecstasy') on the gene expression of the opioid precursor prodynorphin, and on the levels of peptide dynorphin A in the rat brain. Acute (8 mg/kg, intraperitoneally) 3,4-methylenedioxy-N-methylamphetamine markedly raised, two hours later, prodynorphin mRNA levels in the prefrontal cortex, and in the caudate putamen, whereas it decreased gene expression in the ventral tegmental area. Chronic (8 mg/kg, intraperitoneally, twice a day for 7 days) 3,4-methylenedioxy-N-methylamphetamine increased prodynorphin mRNA in the nucleus accumbens, hypothalamus and caudate putamen and decreased it in the ventral tegmental area. Dynorphin A levels increased after chronic treatment in the ventral tegmental area and decreased after acute treatment in the nucleus accumbens, prefrontal cortex and hypothalamus. These findings confirm the role of the dynorphinergic system in mediating the effects of drugs of abuse, such as 3,4-methylenedioxy-N-methylamphetamine, in various regions of the rat brain, which may be important sites for the opioidergic mechanisms activated by addictive drugs.
强啡肽原系统与精神兴奋剂的神经化学机制有关。接触不同的滥用药物可诱导大脑中的神经适应性变化并影响阿片样物质基因表达。本研究旨在探讨药物成瘾过程中存在共同神经生物学底物的可能性。我们研究了单次和重复给予3,4-亚甲基二氧基-N-甲基苯丙胺（“摇头丸”）对阿片样物质前体强啡肽原的基因表达以及大鼠脑中强啡肽A肽水平的影响。急性给予（8毫克/千克，腹腔注射）3,4-亚甲基二氧基-N-甲基苯丙胺两小时后，前额叶皮质和尾状壳核中的强啡肽原mRNA水平显著升高，而腹侧被盖区的基因表达则降低。慢性给予（8毫克/千克，腹腔注射，每天两次，共7天）3,4-亚甲基二氧基-N-甲基苯丙胺可使伏隔核、下丘脑和尾状壳核中的强啡肽原mRNA增加，而腹侧被盖区的则减少。慢性治疗后腹侧被盖区的强啡肽A水平升高，急性治疗后伏隔核、前额叶皮质和下丘脑的强啡肽A水平降低。这些发现证实了强啡肽能系统在介导滥用药物（如3,4-亚甲基二氧基-N-甲基苯丙胺）对大鼠脑不同区域的作用中的作用，这些区域可能是成瘾药物激活的阿片样物质机制的重要部位。
