Journal
BRAIN RESEARCH
Volume 1059, Issue 1, Pages 20-27Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2005.08.002
Keywords
cannabinoid receptor; morphine; tolerance; glucocorticoid receptor
Categories
Funding
- NIDA NIH HHS [R01 DA08835] Funding Source: Medline
- NINDS NIH HHS [R01 NS45681, R01 NS42661] Funding Source: Medline
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Central cannabinoid receptors (CBRs) have been implicated in the opioid analgesic effects. However, it remains unclear as to whether the expression of central CBRs would be altered after repeated morphine exposure. Here, we show that chronic intrathecal treatment with morphine (10 mu g, twice daily or 6 days) induced a time-dependent upregulation of both CB-1 and CB-2 receptors within the spinal cord dorsal horn. This morphine-induced CB-1 and CB-2 upregulation was dose-dependently attenuated by the intrathecal co-administration of morphine with the glucocorticoid receptor (GR) antagonist RU38486 (0.25, 0.5, or 2 mu g). The intrathecal RU38486 treatment regimen also attenuated the development of morphine tolerance. These results indicate that the expression of spinal CBRs was altered following repeated morphine exposure and regulated by the activation of central GRs. (c) 2005 Elsevier B.V. All rights reserved.
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