Behavioural and morphological evidence for the involvement of glial cell activation in delta opioid receptor function: implications for the development of opioid tolerance.
Previous studies have demonstrated that prolonged morphine treatment in vivo induces the translocation of delta opioid receptors (deltaORs) from intracellular compartments to neuronal plasma membranes and this trafficking event is correlated with an increased functional competence of the receptor. The mechanism underlying this phenomenon is unknown; however chronic morphine treatment has been shown to involve the activation and hypertrophy of spinal glial cells. In the present study we have examined whether activated glia may be associated with the enhanced deltaOR-mediated antinociception observed following prolonged morphine treatment. Accordingly, animals were treated with morphine with or without concomitant administration of propentofylline, an inhibitor of glial activation that was previously shown to block the development of morphine antinociceptive tolerance. The morphine regimen previously demonstrated to initiate deltaOR trafficking induced the activation of both astrocytes and microglia in the dorsal spinal cord as indicated by a significant increase in cell volume and cell surface area. Consistent with previous data, morphine-treated rats displayed a significant augmentation in deltaOR-mediated antinociception. Concomitant spinal administration of propentofylline with morphine significantly attenuated the spinal immune response as well as the morphine-induced enhancement of deltaOR-mediated effects. These results complement previous reports that glial activation contributes to a state of opioid analgesic tolerance, and also suggest that neuro-glial communication is likely responsible in part for the altered functional competence in deltaOR-mediated effects following morphine treatment.
Holdridge
Sarah V
SV
Department of Pharmacology & Toxicology, Queen's University, Kingston, Ontario, Canada. 9svh@qlink.queensu.ca
Armstrong
Stacey A
SA
Taylor
Anna M W
AM
Cahill
Catherine M
CM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D004361:Drug Tolerance / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D000700:Analgesics; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D014970:Xanthines; C060209:deltorphin II, Ala(2)-; C032114:propentofylline; D009020:Morphine