Adenosine receptor antagonists inhibit the development of morphine sensitization in the C57BL/6 mouse.
We examined the effects of adenosine antagonists on the development of morphine sensitization in C57BL/6 mice. Adenosine antagonists or vehicle were repeatedly co-administered intraperitoneally with morphine (10 mg/kg, s.c.) to mice once every other day for 9 days. Two days later, a 10 mg/kg morphine-only challenge was administered to each group. Consistent with sensitization, mice receiving morphine alone developed enhanced ambulatory activity responses to subsequent morphine administrations and, upon morphine-only challenge, had a significantly greater response to morphine than vehicle pretreated animals. The nonselective adenosine antagonist, caffeine, at 10 and 20 mg/kg but not at 5 mg/kg, attenuated the development of sensitization during co-administration with morphine and also following morphine-only challenge. The adenosine A1 selective antagonist 1,3-dipropyl-8-(2-amino-4-chlorophenyl)-xanthine (PACPX), at 0.001 and 0.002 mg/kg but not at 0.2 mg/kg, similarly attenuated the development of morphine sensitization. We propose a mechanism which involves an adenosine receptor role in the mesolimbic dopamine system.
D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004338:Drug Combinations; D004351:Drug Resistance; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines / Q000494:pharmacology