FIGURE 4

Effects of treatment with memantine during extinction on morphine-induced reinstatement of extinguished place preference (a) and locomotor activity (b). During the extinction phase, morphine-conditioned groups and vehicle-conditioned control group were treated with saline or memantine and exposed to the arms as described in the legend to Figure 3. Test 2 revealed that all morphine-conditioned groups extinguished place preference response. Before test 3, mice were challenged with 1 mg/kg of morphine. (a) Two-way ANOVA demonstrated significant interaction between treatment and test number: F(6,62)=5.079, P<0.001. Separate between-subject ANOVAs for tests 1, 2, and 3 revealed the following effects of treatment: F(3,31)=6.077, 0.73, and 5.638 (P<0.01, NS and P<0.01), respectively. Post hoc tests demonstrated significant effects of conditioning with morphine on test 1 (significance toward group 'vehicle-conditioned/extinguished with 7.5 mg/kg of memantine/morphine-challenged'; ^## P<0.01, ^### P<0.001), and effects of treatment with memantine (7.5 mg/kg) during extinction as evaluated during test 3 (significance toward group 'morphine-conditioned/saline-extinguished/morphine-challenged'; ^* P<0.05, ^*** P<0.001). (b) Two-way ANOVA on locomotor activity data (that ranged from 13.621.87 entrances on test 3 in morphine-conditioned/7.5 mg/kg memantine-extinguished/morphine-challenged to 31.114.28 entrances on test 3 in morphine-conditioned/saline-extinguished/morphine-challenged) revealed significant effect of the interaction between the test number and treatment F(6,62)=4.106, P<0.01. Separate between-subject ANOVAs for locomotor activity data on tests 1, 2, and 3 revealed the following effects of treatment: F(3,31)=0.312, 2.309, and 4.354 (NS, NS and P<0.05), respectively. Post hoc Duncan's tests demonstrated significant effects of treatment with memantine 7.5 mg/kg during extinction on locomotor activity of morphine-challenged mice revealed on test 3 (significance toward group 'morphine-conditioned/saline-extinguished/morphine-challenged'; ^* P<0.05).