Effect of estrogen upon methamphetamine-induced neurotoxicity within the impaired nigrostriatal dopaminergic system.
In the present study, we investigated whether estrogen remains effective as a neuroprotectant within an impaired nigrostriatal dopaminergic (NSDA) system of gonadectomized female and male mice. In Experiment 1, mice were treated with four different regimens of methamphetamine (MA) to establish a protocol for an impaired NSDA system to be used in subsequent experiments. Based upon the results of Experiment 1, in Experiment 2 gonadectomized female mice received a treatment with either control (saline), low- or high-dose of MA to produce an initial NSDA impairment. At one week post-MA, mice received either estradiol benzoate (10 microg) or vehicle followed 24 h later with low-MA or saline. Estrogen altered the toxic effects of the second invasion of MA as indicated by a significant decrease in striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations. In addition, DA and DOPAC depletion was greater in high- vs. low-dose MA. In gonadectomized male mice (Experiment 3), striatal DA and DOPAC concentrations showed greater decreases following high-, vs. low-doses of MA; however, estrogen did not alter these responses. These results demonstrate that the capacity for estrogen to protect or worsen MA-induced neurotoxicity of dopaminergic neurons is limited to female mice and depends on the condition of the NSDA system.
Liu
Bin
B
Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272-0095, USA.
Dluzen
Dean E
DE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D009919:Orchiectomy; D010052:Ovariectomy; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D004967:Estrogens; D018696:Neuroprotective Agents; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D004298:Dopamine