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Effect of estrogen upon methamphetamine‐induced neurotoxicity within the impaired nigrostriatal dopaminergic system
Author(s) -
Liu Bin,
Dluzen Dean E.
Publication year - 2006
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.20307
Subject(s) - dopaminergic , methamphetamine , estrogen , nigrostriatal pathway , estradiol benzoate , medicine , endocrinology , dopamine , neurotoxicity , dopaminergic pathways , saline , pharmacology , substantia nigra , toxicity , ovariectomized rat
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 μg) 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. Synapse 60:354–361, 2006. © 2006 Wiley‐Liss, Inc.