Methamphetamine neurotoxicity and striatal glutamate release: comparison to 3,4-methylenedioxymethamphetamine.
The effect of repeated administration of either methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA) or vehicle on the extracellular concentrations of glutamate (GLU), aspartate, taurine, dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was studied in awake, freely moving rats using in vivo microdialysis. MA (7.5 mg/kg, i.p.) administered every 2 h for a total of 3 injections, increased the extracellular concentration of GLU in the anteromedial striatum. By contrast, neither vehicle nor MDMA (9.2 and 13.8 mg/kg) increased GLU efflux following repeated administration. Both MA and MDMA increased the extracellular concentration of DA in the striatum. However, the cumulative increase in DA was significantly greater in the MDMA treated animals as compared to the MA group. The concentrations of DA, serotonin (5-HT) and their metabolites were determined in the striatum 7 days following the repeated administration of MA, MDMA and vehicle. MA, but not MDMA or vehicle, decreased the concentration of DA in the striatum. Conversely, MDMA (13.8 mg/kg) decreased the concentration of 5-HT, whereas MA, MDMA (9.2 mg/kg) and vehicle had no effect on striatal 5-HT content. These data are suggestive that the long-term (7 day) DA neurotoxicity produced by the repeated administration of MA is mediated, in part, by a delayed increase in extracellular concentrations of GLU. In contrast, repeated administration of MDMA, at a dose which produced a long-term (7 day) depletion of striatal 5-HT content, had no effect on GLU efflux in the striatum.
Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-5000.
J F
JF
Nash
B K
BK
Yamamoto
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015198:Designer Drugs; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013654:Taurine / Q000378:metabolism; D013997:Time Factors
D015198:Designer Drugs; D005971:Glutamates; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D013654:Taurine; D001224:Aspartic Acid; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine