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題 名 | U-50488 Decreases the Rewarding Effect and Mesolimbic Dopamine Neuron Activity Induced by Morphine in Rats=U-50488降低嗎啡在大鼠所引起的酬賞效果及中邊緣多巴胺神經活性 |
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作 者 | 黃翊恭; 蕭翔仁; 呂偉明; 陶寶綠; | 書刊名 | Journal of Medical Sciences |
卷 期 | 27:1 2007.02[民96.02] |
頁 次 | 頁15-21 |
分類號 | 416.5 |
關鍵詞 | 嗎啡; 酬賞效果; Morphine; U-50488; Microdialysis; Nucleus accumbens; Mesolimbic pathway; |
語 文 | 英文(English) |
英文摘要 | Background: Morphine is one of the most effective analgesics used to treat postoperative or cancer pain. A major drawback of its continuous use is the development of tolerance and dependence. U-50488, a selective κ-opioid receptor agonist has been reported to suppress the development of antinociceptive tolerance to morphine in animals. Here we further investigated its effect on morphine addiction. Methods: Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors associated with psychological dependence in Sprague Dawley rats. Microdialysis and high-performance liquid chromatography were used to determine the extracellular level of dopamine metabolites in the shell region of the nucleus accumbens (NAc). Results: Coadministered U-50488 was able to abolish both the CPP effect and behavioral sensitization induced by morphine. A significant increase of dopamine metabolites following morphine administration was demonstrated in the NAc. This increase by morphine could be attenuated by coadministered U-50488, whereas U-50488 itself did not show significant effects. Conclusions: U-50488 might effectively attenuate morphine-induced psychological dependence. Neurochemical analysis suggested that U-50488 could be acting by inhibiting the dopaminergic mesolimbic pathway activated by morphine, which is believed to cause rewarding. |
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