Figure 8.

Effects of chronic treatment of mice with equal daily dose of morphine (20 mg/kg, twice per day) on adenosine uptake, extracellular adenosine accumulation in the hippocampus, and retention of spatial memory. A, B, Chronic exposure of mice to a lower but constant dose morphine significantly increased extracellular adenosine concentration and decreased the uptake of [³H]adenosine at 2 h and 7 d but not 30 d. Data are represented as mean ± SEM (n = 5–6). *p < 0.05, **p < 0.01 compared with saline-treated control mice, Student's t test. C, Mice chronically treated with a lower but constant dose morphine took more time to cross the location of platform at 2 h and 7 d but not 30 d after last morphine administration. Data are represented as mean ± SEM (n = 9). *p < 0.05 compared with saline-treated control mice; ^#p < 0.05 compared with mice treated with morphine alone, two-way ANOVA test. D, E, Mice chronically treated with a lower but constant dose morphine spontaneously expressed somatic opiate withdrawal signs 8, 12, 24, and 36 h but not 2 h and 7 d after the last morphine administration. Data are represented as mean ± SEM (n = 8). *p < 0.05, **p < 0.01 compared with saline-treated control mice, two-way ANOVA with PLSD post hoc test. CTL, Control; MOR, morphine.