NMDAR1 antisense attenuates morphine tolerance For days 1 to 5, treatments were twice a day (9:00 AM and 5:00 PM) and consisted of the i.t. administration of 5 μ l of saline, 30 nM NMDAR1 antisense ODN, or 30 nM mismatch ODN. For days 6 to 8, the ODN or saline treatment was twice a day (9:00 AM and 5:00 PM) and consisted of the i.t. administration of 5 μ l of saline, 30 nM NMDAR1 antisense, or 30 nM mismatch ODN. Morphine treatment was three times a day (10:00 AM, 3:00 PM, and 6:00 PM) and consisted of the i.t. administration of morphine (10, 20, or 40 μ g on days 6 to 8, respectively) or saline. On day 6, the 10:00 AM morphine dose was replaced with a CDR assessment of the morphine ED50 values. On day 9, only the AM dose of ODN or saline was administered. On day 10, the morphine CDR was repeated.
| Treatment | Day | Morphine ED50 | 95% CI | Relative Potency |
|---|---|---|---|---|
| μg/rat | ||||
| Saline + saline | 6 | 1.3 | 0.7–2.5 | 1.00 |
| Saline + morphine | 6 | 1.1 | 0.7–1.5 | 1.18 |
| Antisense + morphine | 6 | 1.6 | 1.1–2.2 | 0.81 |
| Mismatch + morphine | 6 | 1.6 | 1.1–2.3 | 0.81 |
| Saline + saline | 10 | 0.9 | 0.5–1.9 | 1.44 |
| Saline + morphine | 10 | 30.3* | 21.7–42.7 | 0.04 |
| Antisense + morphine | 10 | 8.1*,** | 5.9–11.0 | 0.16 |
| Mismatch + morphine | 10 | 22.7* | 16.1–32.1 | 0.06 |