Differential effect of dietary selenium on the long-term neurotoxicity induced by MDMA in mice and rats.
We examined the effect of dietary selenium (Se) on the long-term effect of 3,4-methylenedioxymethamphetamine (MDMA) on dopamine (DA) and 5-hydroxytryptamine (5-HT) containing neurons in the brain of mice and rats. Animals were fed either a Se-deficient (<0.02 ppm) or Se-replete (0.2 ppm) diet for 8 weeks. On the seventh week mice received three injections of MDMA (15 mg/kg, i.p. 3 h apart) or saline and rats a single dose of MDMA (12.5 mg/kg i.p.) or saline. All animals were sacrificed 7 days later. MDMA administration to mice depleted striatal DA concentration in both dietary groups, although depletion was considerably larger in the Se-deficient mice (64%) than Se-replete mice (30%). In addition, a decrease in 5-HT (17-32%) occurred in brain regions of Se-deficient but not Se-replete mice. In rats, MDMA decreased cortical [(3)H]-paroxetine binding (62%) and 5-HT content, the depletion being similar in the Se-deficient and Se-replete groups. No DA loss occurred in either group. There was no difference in the hyperthermic response induced by MDMA in Se-deficient or Se-replete animals. The Se-deficient diet decreased glutathione peroxidase (GPx) activity by 30% in mouse striatum and cortex and increased the degree of lipid peroxidation in cortical synaptosomes. Se-deficient rats also showed a decrease in brain GPx activity compared with the Se-replete group, but the degree of lipid peroxidation in synaptosomes was similar in both dietary groups. These results suggest that the antioxidant capacity of rats and mice differ leading to a differential susceptibility to the oxidative stress caused by MDMA in situations of low dietary Se.
Sanchez
V
V
Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain.
Camarero
J
J
O'Shea
E
E
Green
A R
AR
Colado
M I
MI
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004032:Diet; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D051381:Rats; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D015430:Weight Gain / Q000187:drug effects
D012701:Serotonin; D005979:Glutathione Peroxidase; D012643:Selenium; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine