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Effects of lubeluzole on the methamphetamine‐induced increase in extracellular glutamate and the long‐term depletion of striatal dopamine
Author(s) -
Wallace Tanya L.,
Vorhees Charles V.,
Gudelsky Gary A.
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1030
Subject(s) - dopamine , extracellular , glutamate receptor , microdialysis , methamphetamine , striatum , pharmacology , neurotransmitter , extracellular fluid , chemistry , neuroscience , biology , biochemistry , central nervous system , receptor
The administration of a neurotoxic regimen of methamphetamine (MA) produces an acute elevation in the extracellular concentrations of dopamine and glutamate in the striatum and a long‐term depletion of striatal dopamine content in rats. The intent of the present study was to determine whether attenuation of the MA‐induced increase in extracellular glutamate would prevent the depletion of striatal dopamine. Male rats were treated with MA (10 mg/kg, i.p.) or vehicle every 2 h for four injections and concomitantly perfused intrastriatally with either artificial cerebrospinal fluid or lubeluzole (300 μM), a novel neuroprotectant that has been shown to prevent the increase in extracellular glutamate after the induction of neocortical infarct in rats. Lubeluzole significantly attenuated the MA‐induced increase in extracellular glutamate in the striatum without affecting the MA‐induced increase in extracellular dopamine or the MA‐induced hyperthermic response. Nevertheless, lubeluzole did not prevent the long‐term depletion of striatal dopamine produced by a neurotoxic regimen of MA. These results suggest that the MA‐induced depletion of striatal dopamine may not be dependent on the increased extracellular concentration of striatal glutamate. Synapse 40:95–101, 2001. © 2001 Wiley‐Liss, Inc.