Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 257; no. 1; pp. 262 - 270
• Main Authors: J F Bowyer, A C Scallet, R R Holson, G W Lipe, W Slikker, Jr, S F Ali
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.04.1991
• Subjects: 550201 - Biochemistry- Tracer Techniques; ALKALINE EARTH METAL COMPOUNDS; AMIDES; AMINES; AMINO ACIDS; AMPHETAMINES; ANALEPTICS; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BASIC BIOLOGICAL SCIENCES; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; BODY; BRAIN; CARBOXYLIC ACIDS; CARDIOTONICS; CARDIOVASCULAR AGENTS; CATIONS; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM AGENTS; CHARGED PARTICLES; Corpus Striatum - secretion; Dizocilpine Maleate - pharmacology; DOPAMINE; Dopamine - secretion; Drug toxicity and drugs side effects treatment; DRUGS; Glutamates - pharmacology; GLUTAMIC ACID; GLUTAMINE; Glutamine - pharmacology; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; IN VITRO; In Vitro Techniques; IONS; ISOTOPE APPLICATIONS; KINETICS; Magnesium - pharmacology; MAGNESIUM COMPOUNDS; Male; MAMMALS; Medical sciences; Methamphetamine - toxicity; NERVES; NERVOUS SYSTEM; NEUROREGULATORS; Nomifensine - pharmacology; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; Pharmacology. Drug treatments; PHENOLS; POLYPHENOLS; RATS; Rats, Inbred Strains; REACTION KINETICS; Receptors, N-Methyl-D-Aspartate - drug effects; RODENTS; SECRETION; SYMPATHOMIMETICS; Toxicity: nervous system and muscle; TRACER TECHNIQUES; Tritium; TRITIUM COMPOUNDS; VERTEBRATES; Amphetamine derivatives; Brain; Dopamine; CNS stimulant; Psychotropic; Toxicity; Central nervous system; Corpus striatum; Glutamate; In vitro; Prevention; Excitatory aminoacid; Drug interaction; Mechanism of action; Release; Glutamine
• ISSN: 0022-3565; 1521-0103

The interactions of MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine], glutamate and glutamine with methamphetamine (METH)-evoked release of [3H]dopamine were assessed in vitro to determine whether MK-801 inhibition of METH neurotoxicity might be mediated presynaptically, and to evaluate the effects of glutamatergic stimulation on METH-evoked dopamine release. MK-801 inhibition of glutamate- or METH-evoked dopamine release might reduce synaptic dopamine levels during METH exposure and decrease the formation of 6-hydroxydopamine or other related neurotoxins. Without Mg++ present, 40 microM and 1 mM glutamate evoked a N-methyl-D-aspartate receptor-mediated [3H]dopamine and [3H]metabolite (tritium) release of 3 to 6 and 12 to 16% of total tritium stores, respectively, from striatal slices. With 1.50 mM Mg++ present, 10 mM glutamate alone or in combination with the dopamine uptake blocker nomifensine released only 2.1 or 4.2%, respectively, of total tritium stores, and release was only partially dependent on N-methyl-D-aspartate-type glutamate receptors. With or without 1.50 mM Mg++ present, 0.5 or 5 microM METH evoked a substantial release of tritium (5-8 or 12-21% of total stores, respectively). METH-evoked dopamine release was not affected by 5 microM MK-801 but METH-evoked release was additive with glutamate-evoked release. Without Mg++ present, 1 mM glutamine increased glutamate release and induced the release of [3H]dopamine and metabolites. Both 0.5 and 5 microM METH also increased tritium release with 1 mM glutamine present. When striatal slices were exposed to 5 microM METH this glutamine-evoked release of glutamate was increased more than 50%.