Summary
Following intraperitoneal administration of the non-competitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801), levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in mouse striatum and limbic forebrain. When dizocilpine was given to animals treated with NSD 1015, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase and monoamine oxidase, there was an increase in levels of DOPA and 3-methoxytyramine (3-MT). These findings suggest that dizocilpine stimulates DA synthesis and release in mouse brain. Following dizocilpine treatment a clear-cut increase in spontaneous locomotor activity was observed, probably partly due to enhanced dopaminergic tone. The competitive NMDA antagonist D-CPPene produced locomotor stimulation as well, but in contrast to following dizocilpine treatment levels of 3-MT decreased. Thus the stimulation of locomotor activity following D-CPPene treatment does not seem to be mediated through activation of central dopaminergic systems. However, haloperidol pretreatment antagonized this locomotor response, indicating that the dopaminergic system plays a permissive role in this context.
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Svensson, A., Pileblad, E. & Carlsson, M. A comparison between the non-competitive NMDA antagonist dizocilpine (MK-801) and the competitive NMDA antagonist D-CPPene with regard to dopamine turnover and locomotor-stimulatory properties in mice. J. Neural Transmission 85, 117–129 (1991). https://doi.org/10.1007/BF01244704
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DOI: https://doi.org/10.1007/BF01244704