Section 42
Chapter 41,564

The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice

Carlsson, M.; Carlsson, A.

Journal of Neural Transmission 75(3): 221-226


PMID: 2538557
DOI: 10.1007/bf01258633
Accession: 041563300

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It was shown in the present study that the selective non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] caused a pronounced and dose-dependent increase in locomotion in mice pretreated with a combination of reserpine and alpha-methyl-para-tyrosine. Haloperidol pretreatment did not antagonize the MK-801-induced stimulation of locomotion. The findings are discussed in relation to the concept of a corticostriatothalamocortical negative feedback loop serving to protect the cortex from an overload of information and hyperarousal. Such a feedback loop would encompass i.a. corticostriatal glutamatergic neurons and it would be modulated by mesencephalostriatal dopaminergic neurons.

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