title: The effect of chronic administration of caffeine on morphine-induced analgesia, tolerance and dependence in mice.
abstract: Morphine-induced analgesia, and the development of morphine-induced tolerance and dependence was determined in mice which had drunk caffeinated water (1 mg/ml) for 14 days or in mice which had received (-)-N6-(phenylisopropyl)-adenosine (PIA) 1 mg/kg i.p. for 14 days. Analgesia was assessed by the tail flick assay. The development of dependence was assessed by determining the ED50 of naloxone to precipitate withdrawal jumping (3 h after 100 mg/kg morphine pretreatment or 72 h after s.c. implantation of a morphine 75 mg pellet) and by determining the extent of naloxone-precipitated hypothermia in morphine-implanted animals. In mice chronically administered caffeine, the ED50 for morphine-induced analgesia was significantly decreased while the naloxone ED50 for withdrawal jumping increased by 2-fold after both types of morphine pretreatment. In control animals (tap water for 14 days), doses of 1 and 10 mg/kg of naloxone caused significant hypothermia in morphine-implanted animals. Doses of naloxone up to 100 mg/kg did not cause significant hypothermia in morphine-implanted animals which had received chronic caffeine. The development of tolerance was determined by computing the morphine potency ratio for the tail flick assay (tolerant ED50/control ED50). In mice chronically administered caffeine, the potency ratio was decreased significantly in morphine-implanted animals when compared to control. Morphine-induced analgesia, tolerance and dependence was not changed significantly in animals chronically administered PIA. Neither the distribution of morphine to the brain nor the opioid receptor binding parameters for [3H]etorphine and [3H]naltrexone were altered in mice chronically administered caffeine or PIA.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000698:Analgesia; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D009021:Morphine Dependence; D009270:Naloxone / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects
chemical_list: D011957:Receptors, Opioid; D010660:Phenylisopropyladenosine; D009270:Naloxone; D002110:Caffeine; D009020:Morphine