کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4347506 1296845 2009 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The contribution of MOR-1 exons 1–4 to morphine and heroin analgesia and dependence
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
The contribution of MOR-1 exons 1–4 to morphine and heroin analgesia and dependence
چکیده انگلیسی

Although morphine and heroin analgesia is mediated by μ-opioid receptors encoded by the MOR-1 gene, distinct isoforms are involved. Both opioids also induce dependence by acting at μ-opioid receptors, but which variants are utilized is not known. Here, we assayed morphine and heroin analgesia and dependence in mice treated with antisense oligodeoxynucleotides (AO) targeting MOR-1 exons 1–4. Whereas AOs targeting exons 1 and 4 blocked morphine analgesia, those targeting exons 2 and 3 blocked heroin analgesia. Neither morphine nor heroin analgesia was compromised 5 days after the last AO injection. In morphine and heroin dependent mice, only exon 1 AO significantly reduced jumping incidence during naloxone (50 mg/kg) precipitated withdrawal. Neither analgesia nor withdrawal jumping was attenuated in controls pretreated with saline or a mismatch oligodeoxynucleotide control sequence. While these data confirm previous reports that morphine and heroin analgesia are not mediated by a single μ-opioid receptor, both opiates nonetheless apparently induce dependence via a μ-opioid receptor isoform containing exon 1. For heroin, the possibility that analgesia and dependence are mediated by distinct μ-opioid receptor isoforms offers the prospect of developing potent opiate analgesics possessing reduced dependence liability.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 457, Issue 3, 3 July 2009, Pages 115–119
نویسندگان
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