Figure 5.

Effect of NOArg and antisense on morphine tolerance. (a) Groups of mice received NOArg (1 μg, i.c.v.) or vehicle daily along with morphine (5 mg/kg, s.c.). Analgesia was tested at the indicated times. After 4 days of morphine, the NOArg group was significantly higher than the control (P < 0.002). (b) Groups of mice (n ≥ 10) received the indicated saline, antisense F (20 or 5 μg, i.c.v.), or mismatch F treatment every other day for a total of four treatments, starting 3 days before the initiation of the chronic morphine dosing. On day 1, the day of the third antisense or mismatch treatment, all groups started receiving daily morphine injections (5 mg/kg, s.c.) and were tested for analgesia. On day 5, the mismatch and control groups were significantly different from both doses of antisense F (20 μg, P < 0.001; 5 μg, P < 0.005). (c) Groups of mice (n = 10) received three injections of saline or an antisense (5 μg, i.c.v.) targeting iNOS (5′-GAT CCT GCC GAT GCA GCG AG-3′; GenBank accession no. M92649) on alternate days. Mice started receiving morphine (5 mg/kg, s.c.) on the last day of antisense treatment. The time on the figure refers to the days of morphine treatment. The iNOS antisense had no effect upon the development of morphine tolerance.