Effects of chronic treatment of mice with increasing doses of morphine (20–100 mg/kg) for 7 consecutive days on adenosine uptake, extracellular adenosine accumulation, and three adenosine metabolism enzyme activities. A, Chronic morphine treatment significantly increased the extracellular adenosine concentrations in hippocampal slices, and this effect could be prevented by concomitant injection of opioid receptor antagonist naltrexone (4 mg/kg, i.p.). B, Chronic morphine treatment significantly inhibited [3H]adenosine uptake in hippocampal synaptosomes, and this effect could also be prevented by opioid receptor antagonist naltrexone. C, Chronic morphine treatment had no significant effect on the activities of three crucial adenosine metabolism enzymes in the hippocampus. Data represent the mean ± SEM (n = 4). **p < 0.01 compared with saline-treated control mice; ##p < 0.01 compared with mice treated with morphine alone (n = 8), two-way ANOVA test. CTL, Control; MOR, morphine; NAL, naltrexone.