Time course effects of MK-801: the relationship between brain neurochemistry and behavior

Separate groups of rats were given saline or MK-801 treatments (0.3 mg/kg) and tested for locomotion activity levels for 10 min at 30, 60, and 120 min postinjection. At each postinjection time interval the MK-801 rats exhibited a marked hyperactivity that was unchanged across the three postinjection intervals. Ex vivo biochemical assays were performed to assess the neurochemical effects of MK-801 at each injection interval. In the striatum, a marked increase in dopamine metabolism was observed in the 120 injection group, but, otherwise, no other changes in striatum were detected. In contrast, a significant increase in dopamine metabolism was observed after 30 min in the medial prefrontal cortex, and this effect persisted across all postinjection intervals. At 120 min, however, the biochemical impact of the MK-801 treatment on medial prefrontal cortex broadened to include a decrease in purine metabolism and norepinephrine. Serotonin metabolism was unaffected in striatum or medial prefrontal cortex across all injection intervals, and there was no effect of MK-801 on plasma corticosterone levels.