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MK-801 Increases Extracellular 5-Hydroxytryptamine in Rat Hippocampus and Striatum In Vivo


Address correspondence and reprint requests to Dr. P. S. Whitton at The Department of Pharmacology, The School of Pharmacy, 29–39 Brunswick Square, London WC1N 1AX, U.K.


Abstract: The effect of MK-801 (0.25 or 0.5 mg/kg) on the extracellular concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat hippocampus and striatum was studied using intracerebral dialysis. The dialysate 5-HT concentration was dose-dependently increased by MK-801 in both regions. In the hippocampus, at the higher drug dose a slow increase in the 5-HIAA level was observed, and this became significant 3 h after treatment. In contrast to this, the extracellular 5-HIAA content in the striatum was significantly decreased 150 min after administration of both doses of MK-801. The data are discussed in the light of the known behavioural effects of MK-801 and possible N-methyl-d-aspartic acid receptor regulation of 5-HT release.