Functional consequences following methamphetamine-induced neuronal damage.
The functional consequences following methamphetamine-induced neuronal damage were evaluated under several different conditions known to affect the magnitude of the lesion. It was found that methamphetamine (6.25 mg/kg administered SC, four times at 2-h intervals) caused long-lasting depletions of striatal dopamine and serotonin and that pretreatment with the antioxidant, ascorbic acid (100 mg/kg), attenuated these depletions, whereas pretreatment with the superoxide dismutase inhibitor diethyldithiocarbamate (200 mg/kg) exacerbated these depletions. The dopamine depletions resulting from the repeated administration of methamphetamine under these various conditions did not result in any alteration in the consumption of a sweetened-condensed milk solution under baseline conditions. However, when these lesioned animals were challenged with acutely administered methamphetamine, it was observed that there was an altered sensitivity to the milk intake decreasing effects of this compound. That is, the degree to which the acutely administered methamphetamine reduced the intake of sweetened-condensed milk was highly correlated with the magnitude of the methamphetamine-induced dopamine and serotonin depletions. These observations support the hypothesis that methamphetamine-induced neuronal damage is mediated by free radical formation and indicate that behavioral measures may be employed to assess neuronal damage.
De Vito
M J
MJ
Department of Toxicology, Rutgers, State University, New Brunswick, NJ 08903.
Wagner
G C
GC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology / Q000523:psychology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D008694:Methamphetamine; D004298:Dopamine