Effects of lubeluzole on the methamphetamine-induced increase in extracellular glutamate and the long-term depletion of striatal dopamine.
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 microM), 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.
Wallace
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TL
Neuroscience Graduate Program, University of Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267-0004, USA.
Vorhees
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CV
Gudelsky
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GA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology
D018696:Neuroprotective Agents; D010880:Piperidines; D015222:Sodium Channels; D013844:Thiazoles; D018698:Glutamic Acid; D008694:Methamphetamine; D014701:Veratridine; C097722:lubeluzole; D004298:Dopamine