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. 2001 Sep 25;98(20):11047–11054. doi: 10.1073/pnas.191353298

Figure 3.

Figure 3

Attenuation of the hypolocomotor effect of d-amphetamine in DAT-KO mice by (+)-MK-801. (A) Effect of combined treatment of (+)-MK-801 (0.3 mg/kg, i.p.; administered immediately before exposure to locomotor activity chamber) and d-amphetamine (2 mg/kg, i.p.; 30 min later) on the horizontal activity of DAT-KO mice in a novel environment. Horizontal activity was monitored for 2 h at 5-min intervals; n = 12 for the saline-treated DAT-KO mice (▵), n = 9 for the d-amphetamine-treated DAT-KO (▴), n = 15 for the DAT-KOs given (+)-MK-801 (○), and n = 11 for the DAT-KOs given (+)-MK-801 plus d-amphetamine (●). (+)-MK-801 effectively prevented inhibition of novelty-driven hyperactivity of DAT-KO mice by d-amphetamine. (B) Dose dependence of the effect of (+)-MK-801 on amphetamine induced hypoactivity in DAT-KO mice. Mice were pretreated with saline or different doses of (+)-MK-801 and placed in locomotor activity boxes; 30 min later d-amphetamine (2 mg/kg, i.p.) was administered. Horizontal activity was further monitored every 5 min and presented as cumulative value for 40 min after d-amphetamine administration; n = 7–10 for each group. *, P < 0.05 vs. respective saline- or (+)-MK-801-pretreated controls. (C) Increasing doses of d-amphetamine are able to counteract to effect of (+)-MK-801 in DAT-KO mice. Mice were treated as described in A and B with saline or a single dose of (+)-MK-801 (0.1 mg/kg, i.p.) and 30 min later the effect of saline or various doses of d-amphetamine was tested; n = 6–9 for each group. Data presented as described in B. *, P < 0.05 vs. saline- or (+)-MK-801-pretreated controls, respectively. (D) (+)-MK-801 (0.1 mg/kg, i.p.) reverses hypolocomotor behavior of DAT-KO mice induced by d-amphetamine (2 mg/kg, i.p.). d-Amphetamine was administered 30 min after exposure of mice to the locomotor activity chamber and 30 min later (+)-MK-801 or saline was injected. d-Amphetamine plus saline-treated controls (○), n = 7, and d-amphetamine plus (+)-MK-801-treated mice (●), n = 6. SAL, saline; AMP, amphetamine; MK, (+)-MK-801.