Neuroprotective role of estrogen upon methamphetamine and related neurotoxins within the nigrostriatal dopaminergic system.
Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Drug Interactions; Estrogens/*administration & dosage; Methamphetamine/antagonists & inhibitors/*toxicity; Neurotoxins/antagonists & inhibitors/*toxicity; Substantia Nigra/*drug effects/metabolism; Time Factors
In this report we describe some of the data on the capacity for estrogen to function as a neuroprotectant of the nigrostriatal dopaminergic (NSDA) system. The data show that estrogen (E) can alter two different response characteristics to NSDA neurotoxins. The first being that striatal DA concentrations of ovariectomized rodents treated with E are consistently greater than non-E-treated animals in response to neurotoxins which produce degeneration of the NSDA system. The second being that E significantly reduces the amount of DA output upon initial exposure to the NSDA neurotoxin, 1-methyl-4-phenylpyridium ion (MPP+). At present, it is not known whether these two response characteristics are related. An intriguing possibility is that the E-dependent changes in initial DA output are related to the resultant neurotoxicity (attenuations in DA concentration reductions). So far our incipient findings do not seem to support this eventuality. However, additional testing on this topic is required. The present data suggest that one of the mechanisms by which E can exert these effects is through inhibition of DAT activity. This conclusion results from data which show that E produces: 1) an inhibition of [3H]DA uptake, 2) a reduction in DA clearance rates, and 3) an effect upon DA recovery that is similar to that observed to the putative DA uptake blocker, nomifensine. The capacity and significance for steroid hormones to modulate neurotransmitter transporters has been recently reviewed.
Dluzen D E; McDermott J L
Annals of the New York Academy of Sciences
2000
2000-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/j.1749-6632.2000.tb05189.x" target="_blank" rel="noreferrer noopener">10.1111/j.1749-6632.2000.tb05189.x</a>
Acute effects of estrogen upon methamphetamine induced neurotoxicity of the nigrostriatal dopaminergic system.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Animals; Dopamine/metabolism; Drug Interactions; Estrogens/metabolism/*pharmacology; Female; Methamphetamine/antagonists & inhibitors/*toxicity; Mice; Neostriatum/*drug effects/metabolism/physiopathology; Neural Pathways/*drug effects/metabolism/physiopathology; Neuroprotective Agents/metabolism/pharmacology; Neurotoxins/antagonists & inhibitors/toxicity; Ovariectomy; Parkinson Disease/drug therapy/metabolism/physiopathology; Presynaptic Terminals/drug effects/metabolism; Reaction Time/drug effects/physiology; Sex Factors; Substantia Nigra/*drug effects/metabolism/physiopathology
Estrogen acts as a neuroprotectant of the nigrostriatal dopaminergic system when given chronically to female mice prior to Methamphetamine (MA) insult. In this report, we tested the acute effects of Estradiol Benzoate (EB-10 microg in Oil) in ovariectomized CD-1 mice to function as a neuroprotectant when administered prior to (Experiment 1) or after (Experiment 2) MA treatment. Striatal dopamine (DA) concentrations and DOPAC/DA ratios were measured to assess the neuroprotective effects of EB. In Experiment 1, we observed that EB exerted a neuroprotective effect upon striatal dopamine concentrations when administered at 24 and 12, but not at 0.5, hours prior to MA injection and upon DOPAC/DA ratios when administered at 24, 12 and 0.5 hours prior to MA. In Experiment 2, no evidence for estrogen to protect the striatum from MA insult was obtained when EB was administered at 15, 30, 60 or 120 minutes after MA. These results show that EB can act as a modulator of MA-induced nigrostriatal dopaminergic neurotoxicity suggestive of a neuroprotectant, when administered within 0.5 hour of MA insult as assessed by measures of DOPAC/DA, but fails to prevent depletion of DA when given after MA insult. The data suggest that estrogen may exert this rapid neuroprotective effect through a non-genomic mechanism.
Gajjar T M; Anderson L I; Dluzen D E
Journal of neural transmission (Vienna, Austria : 1996)
2003
2003-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00702-003-0045-3" target="_blank" rel="noreferrer noopener">10.1007/s00702-003-0045-3</a>