Central glucocorticoid receptors modulate the expression of spinal cannabinoid receptors induced by chronic morphine exposure.
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 microg, twice daily for 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 microg). 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.
Lim
Grewo
G
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street, Boston, MA 02114, USA.
Wang
Shuxing
S
Mao
Jianren
J
D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000187:drug effects* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D009020:Morphine