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.
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.
Department of Pharmacology, University of Göteborg, Sweden.
A
A
Svensson
E
E
Pileblad
M
M
Carlsson
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001923:Brain Chemistry / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D009943:Organophosphorus Compounds; D010879:Piperazines; C065286:SDZ EAA 494; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine