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. 2005 Aug 2;3(8):e271. doi: 10.1371/journal.pbio.0030271

Figure 6. (+)-MDMA Induces Forward Locomotion in DDD Mice.

Figure 6

(A–C) DAT-KO mice were placed in the locomotor activity chamber and 30 min later were treated with αMT (250 mg/kg IP) and 1 h after αMT were challenged with single (B and C) or multiple doses (A) of a drug (interval between treatments is 1 h) (n = 10–16 per group). Repeated treatment with (+)-MDMA (30 and 60 mg/kg IP) induces forward locomotion in DDD mice (A). Analysis of total distance traveled for 1 h after 60 mg/kg IP of (+)-MDMA reveals significant effect of treatment versus respective period in saline-treated controls (p<0.05, two-tailed Mann-Whitney U test, data not shown). Dynamics (B) and dose-response (C) of locomotor effect of (+)-MDMA in DDD mice are shown. Pretreatment with D1 and D2 DA antagonists (SCH23390, 0.1 mg/kg SC plus raclopride, 2 mg/kg IP) 30 min before 100 mg/kg IP (+)-MDMA) did not affect locomotor action of (+)-MDMA (C).

(D) (+)-MDMA (100 mg/kg IP) fails to affect DA dynamics in the striatum of DDD mice as measured by in vivo microdialysis. Data are presented as a percentage of the average level of DA measured in at least three samples collected before αMT administration (n = 4). Analysis of area under curve values for 120-min periods after (+)-MDMA administration revealed no significant difference in comparison with respective values in control group (Figure 1F; p > 0.05, two-tailed Mann-Whitney U test).

(E and F) (+)-MDMA (E) as well as d-amphetamine and d-methamphetamine (F) at moderate doses potentiate locomotor-stimulating effect of subthreshold dose of L-DOPA/carbidopa (10/10 mg/kg IP). DAT-KO mice were treated with αMT as described above (A–C) and 45 min after αMT were injected with amphetamines. L-DOPA/carbidopa was injected 15 min after amphetamines, and distance traveled for 2h was measured (n = 6–15 per group). Note, that no forward locomotion was observed after these doses of (+)-MDMA, d-amphetamine and d-methamphetamine without L-DOPA/carbidopa, whereas L-DOPA/carbidopa (presented as drug dose 0) induced only a modest but significant (p < 0.05) increase in locomotion over saline-treated controls (data not shown).

Single asterisk indicates p < 0.05; double asterisks indicate p < 0.01; and triple asterisks indicate p < 0.001 versus saline-treated controls (C) or L-DOPA/carbidopa-treated (10/10 mg/kg IP) group (E and F) (two-tailed Mann-Whitney U test). d-AMPH, d-amphetamine; METH, d-methamphetamine.