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 morp hine sensitization in C57BL/6 mice. Adenosine antagonists or vehicle were r epeatedly 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 morphin e-only challenge was administered to each group. Consistent with sensitizat ion, mice receiving morphine alone developed enhanced ambulatory activity r esponses to subsequent morphine administrations and, upon morphine-only cha llenge, had a significantly greater response to morphine than vehicle pretr eated animals. The nonselective adenosine antagonist, caffeine, at 10 and 2 0 mg/kg hut not at 5 mg/kg, attenuated the development of sensitization dur ing co-administration with morphine and also following morphine-only challe nge. The adenosine Al selective antagonist 1,3-dipropyl-8-(2-amino-4-chloro phenyl)-xanthine (PACPX), at 0.001 and 0.002 mg/kg but not at 0.2 mg/kg, si milarly attenuated the development of morphine sensitization. We propose a mechanism which involves an adenosine receptor role in the mesolimbic dopam ine system. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.