کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9721086 | 1473271 | 2005 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evidence for a long-term influence on morphie tolerance after previous morphine exposure: role of neuronal glucocorticoid receptors
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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![عکس صفحه اول مقاله: Evidence for a long-term influence on morphie tolerance after previous morphine exposure: role of neuronal glucocorticoid receptors Evidence for a long-term influence on morphie tolerance after previous morphine exposure: role of neuronal glucocorticoid receptors](/preview/png/9721086.png)
چکیده انگلیسی
Opioid analgesic tolerance is a pharmacological phenomenon that overtime diminishes the opioid analgesic effect. However, it remains unknown as to whether a previous opioid exposure would have a long-term influence on opioid tolerance upon subsequent opioid administration. Here, we show that the onset and degree of antinociceptive tolerance to a subsequent cycle of morphine exposure were substantially exacerbated in rats made tolerant to and then recovered from previous morphine administration, indicating a long-term influence from a previous morphine exposure on the development of morphine tolerance. Mechanistically, morphine exposure induced a cyclic AMP and protein kinase A-dependent upregulation of neuronal glucocorticoid receptors (GR) within the spinal cord dorsal horn, which was maintained after discontinuation of morphine administration and significantly enhanced upon a second cycle of morphine exposure. Prevention of the GR upregulation with GR antisense oligonucleotides as well as inhibition of GR activation with the GR antagonist RU38486 effectively prevented the exacerbated morphine tolerance after subsequent cycles of morphine exposure. The results indicate that a previous morphine exposure could induce lasting cellular changes mediated through neuronal GR and influence morphine analgesia upon a subsequent exposure. These findings may have significant implications in clinical opioid therapy and substance abuse.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pain - Volume 114, Issues 1â2, March 2005, Pages 81-92
Journal: Pain - Volume 114, Issues 1â2, March 2005, Pages 81-92
نویسندگان
Grewo Lim, Shuxing Wang, Qing Zeng, Backil Sung, Jianren Mao,