Effects of combined treatment with 10 mg/kg of morphine (10 MS) and a NMDAR antagonist on development and expression of tolerance to antinociceptive effects of MS. Rats received chronic treatment, shown in column titles, b.i.d. for 6 to 7 days, and were tested with cumulative doses of MS in a 55 °C water tail-withdrawal assay before treatment and 12 h after the last injection on Day 6 or 7 of treatment; i.e., on Day 7 (D7) or Day 8 (D8). On test days, rats received saline (SAL) or an appropriate dose of NMDAR antagonist (in milligrams per kilogram) 30 min before tests. Left, dizocilpine (DZ)-MS interaction; right, memantine (MEM)-MS interaction. Other details as in Fig. 2. Text in italics identifies the −30-min pretreatment: SAL saline, 0.1 DZ 0.1 mg/kg dizocilpine, 10 MEM 10 mg/kg memantine