Interactions of MK-801 with glutamate-, glutamine- and methamphetamine-evoked release of [3H]dopamine from striatal slices.
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%.(ABSTRACT TRUNCATED AT 250 WORDS)
Bowyer
J F
JF
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas.
Scallet
A C
AC
Holson
R R
RR
Lipe
G W
GW
Slikker
W
W
Ali
S F
SF
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D005973:Glutamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D014316:Tritium
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D014316:Tritium; D009627:Nomifensine; D018698:Glutamic Acid; D008694:Methamphetamine; D016291:Dizocilpine Maleate; D008274:Magnesium; D004298:Dopamine