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

Figure 4.

Figure 4

Blockade of the hypolocomotor effect of methylphenidate and serotonergic drugs in DAT-KO mice by (+)-MK-801. (A) Effect of (+)-MK-801 (0.3 mg/kg, i.p.) pretreatment on the effect of methylphenidate (30 mg/kg, i.p.) on horizontal activity of DAT-KO mice in a novel environment. DAT-KO mice were pretreated with saline or (+)-MK-801 and 30 min later with methylphenidate as described in Fig. 3 A–C. Horizontal activity was monitored for 2 h at 5-min intervals and presented as cumulative value for 1 h after methylphenidate administration; n = 7–15 for each group. *, P < 0.05 vs. saline- or (+)-MK-801-pretreated controls, respectively. (B) Effect of (+)-MK-801 (0.3 mg/kg, i.p.) pretreatment on the effect of serotonergic drugs on horizontal activity of DAT-KO mice. DAT-KO mice were pretreated with saline or (+)-MK-801 and 30 min later were administered a 5-HT transporter inhibitor (fluoxetine; 20 mg/kg, s.c.), a nonselective 5-HT receptor agonist (quipazine; 3 mg/kg, i.p.), or 5-HT precursor (l-tryptophan; 100 mg/kg, i.p.) as described in Fig. 3 A–C. Horizontal activity was monitored for 2 h at 5-min intervals and presented as cumulative value for 90 min after administration of serotonergic drugs; n = 6–15 for each group. *, P < 0.05 vs. saline- or (+)-MK-801-pretreated controls, respectively. (C) (+)-MK-801 (0.1 mg/kg, i.p.) reverses hypolocomotor behavior of DAT-KO mice induced by l-tryptophan (100 mg/kg, i.p.). l-tryptophan was administered 30 min after exposure of mice to locomotor activity chamber and 30 min later (+)-MK-801 or saline was injected. l-tryptophan plus saline-treated controls (○), n = 7, and l-tryptophan plus (+)-MK-801-treated mice (●), n = 8. SAL, saline; MPH, methylphenidate; TRP, tryptophan.