Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex
Introduction: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of μ-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine&...
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| Format: | Article |
| Language: | English |
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Iran University of Medical Sciences
2016-07-01
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| Series: | Basic and Clinical Neuroscience |
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| Online Access: | http://bcn.iums.ac.ir/browse.php?a_code=A-10-373-3&slc_lang=en&sid=1 |
| _version_ | 1797282524817260544 |
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| author | Shamseddin Ahmadi Fatemeh Rafieenia Jalal Rostamzadeh |
| author_facet | Shamseddin Ahmadi Fatemeh Rafieenia Jalal Rostamzadeh |
| author_sort | Shamseddin Ahmadi |
| collection | DOAJ |
| description | Introduction: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of μ-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at mRNA levels in rat striatum and prefrontal cortex (PFC) after induction of morphine tolerance.
Methods: Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1 gene expression was examined with a semi-quantitative RT-PCR method.
Results: The results showed that long-term morphine a administration induces tolerance to analgesic effect of the opioid, as revealed by a significant decrease in morphine-induced analgesia on day 8 compared to day 1 of the injections (P<0.001). The results also showed that the NR1 gene expression at mRNA level in rats tolerant to morphine was significantly increased in the striatum (P<0.01) but decreased in the PFC (P<0.001).
Conclusion: Therefore, changes in the NR1 gene expression in rat striatum and PFC have a region-specific association with morphine-induced analgesic tolerance. |
| first_indexed | 2024-03-07T17:15:17Z |
| format | Article |
| id | doaj.art-de572504bc164ad8a365e5e8342153be |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T17:15:17Z |
| publishDate | 2016-07-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-de572504bc164ad8a365e5e8342153be2024-03-02T23:28:20ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422016-07-0173241248Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal CortexShamseddin Ahmadi0Fatemeh Rafieenia1Jalal Rostamzadeh2 Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran. Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran. Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran. Introduction: Morphine is a potent analgesic but its continual use results in analgesic tolerance. Mechanisms of this tolerance remain to be clarified. However, changes in the functions of μ-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at mRNA levels in rat striatum and prefrontal cortex (PFC) after induction of morphine tolerance. Methods: Morphine (10 mg/kg, IP) was injected in male Wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1 gene expression was examined with a semi-quantitative RT-PCR method. Results: The results showed that long-term morphine a administration induces tolerance to analgesic effect of the opioid, as revealed by a significant decrease in morphine-induced analgesia on day 8 compared to day 1 of the injections (P<0.001). The results also showed that the NR1 gene expression at mRNA level in rats tolerant to morphine was significantly increased in the striatum (P<0.01) but decreased in the PFC (P<0.001). Conclusion: Therefore, changes in the NR1 gene expression in rat striatum and PFC have a region-specific association with morphine-induced analgesic tolerance.http://bcn.iums.ac.ir/browse.php?a_code=A-10-373-3&slc_lang=en&sid=1Morphine Gene expression Prefrontal cortex Corpus striatum |
| spellingShingle | Shamseddin Ahmadi Fatemeh Rafieenia Jalal Rostamzadeh Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex Basic and Clinical Neuroscience Morphine Gene expression Prefrontal cortex Corpus striatum |
| title | Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex |
| title_full | Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex |
| title_fullStr | Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex |
| title_full_unstemmed | Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex |
| title_short | Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex |
| title_sort | morphine induced analgesic tolerance effect on gene expression of the nmda receptor subunit 1 in rat striatum and prefrontal cortex |
| topic | Morphine Gene expression Prefrontal cortex Corpus striatum |
| url | http://bcn.iums.ac.ir/browse.php?a_code=A-10-373-3&slc_lang=en&sid=1 |
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