The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice.
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.
Carlsson
M
M
Department of Pharmacology, University of Göteborg, Sweden.
Carlsson
A
A
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D015306:Biogenic Monoamines; D003986:Dibenzocycloheptenes; D008781:Methyltyrosines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D019805:alpha-Methyltyrosine; D016291:Dizocilpine Maleate; D012110:Reserpine; D006220:Haloperidol