title: Supraspinal antinociceptive effects of mu and delta agonists involve modulation of adenosine uptake.
abstract: BACKGROUND
  The modulation of extracellular adenosine concentration by opioids provides evidence that the antinociceptive effects of these compounds involve endogenous adenosine. The aim of this study was to determine whether there is a relation between the inhibition of brain synaptosome adenosine uptake by opioid agonists and the analgesic effects of these compounds.
  
  
  METHODS
  The authors used the hot plate and tail-pinch tests to evaluate in mice (C57BL/6 females; weight, 25-30 g) the effects of caffeine, a nonspecific adenosine receptor antagonist, on the antinociceptive effect induced by the intracerebroventricular administration of oxymorphone as a mu agonist, SNC80 as a delta agonist, or U69593 as a kappa agonist. They also investigated the effect of these opioid receptor agonists on the uptake of adenosine by whole brain synaptosomes.
  
  
  RESULTS
  Caffeine decreased the analgesic effects induced by oxymorphone or SNC80 but not those induced by U69593. Oxymorphone and SNC80 inhibited adenosine uptake by brain cells, but U69593 did not.
  
  
  CONCLUSIONS
  The antinociceptive effects obtained with mu or delta (but not kappa) agonists administered supraspinally were indicative of the involvement of modulation of adenosine uptake.
authors.affiliation: UMR CNRS 6560 Faculté de Médecine Secteur Nord, Marseille, France.
authors.forename: Thao
authors.initials: T
authors.lastname: Pham
authors.forename: Louis
authors.initials: L
authors.lastname: Carrega
authors.forename: Nicole
authors.initials: N
authors.lastname: Sauze
authors.forename: Odile
authors.initials: O
authors.lastname: Fund-Saunier
authors.forename: Christiane
authors.initials: C
authors.lastname: Devaux
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Peragut
authors.forename: Alain
authors.initials: A
authors.lastname: Saadjian
authors.forename: Régis
authors.initials: R
authors.lastname: Guieu
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D007267:Injections; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013116:Spinal Cord; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D002110:Caffeine; D000241:Adenosine