Dimebon attenuates methamphetamine, but not MPTP, striatal dopamine depletion.
Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Drug Synergism; Inbred C57BL; Indoles/*pharmacology; Methamphetamine/*pharmacology; Mice
Dimebon is an anti-histamine with central nervous system activity. In this report the effects of dimebon as a neuroprotectant in animal models of Parkinson's disease were tested as assessed in methamphetamine- and MPTP-induced striatal dopaminergic toxicity. Dimebon (1mg/kg) administered at 30 min prior to methamphetamine (40mg/kg) significantly reduced the amount of striatal dopamine depletion in mice, without altering the initial methamphetamine-induced increase in body temperature. In contrast, dimebon at either 1 or 25mg/kg administered at 30 min prior to MPTP (35 mg/kg) was unable to prevent MPTP-induced striatal dopamine loss as determined at 7 days post-methamphetamine/MPTP. These data suggest that dimebon may be exerting a neurotoxin specific neuroprotective effect upon the striatal dopaminergic system and may serve as an important tool for discriminating the mechanistic basis of these two dopaminergic neurotoxins.
Geldenhuys Werner J; Darvesh Altaf S; Dluzen Dean E
Neurochemistry international
2012
2012-06
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/10.1016/j.neuint.2012.03.013" target="_blank" rel="noreferrer noopener">10.1016/j.neuint.2012.03.013</a>
In vivo neurochemical and anatomical heterogeneity of the dopamine uptake system in the rat caudate putamen.
Male; Animals; Rats; Dopamine/*metabolism; Indoles/*pharmacology; Nomifensine/*pharmacology; Homovanillic Acid/metabolism; Electrochemistry; Caudate Nucleus/drug effects/*metabolism; Mazindol/*pharmacology; Neurotransmitter Uptake Inhibitors/*pharmacology; Putamen/drug effects/*metabolism; Inbred Strains; 3; 4-Dihydroxyphenylacetic Acid/metabolism
The neurochemical and anatomical heterogeneity of dopamine uptake blockade was studied at a medial and lateral position in each of 3 rostrocaudal areas of the rat caudate-putamen. In vivo voltammetric measures of extracellular dopamine indicated a lateral-to-medial and rostral-to-caudal gradient in the effect of uptake blockade. The percentage increase in dopamine was greatest in the rostrolateral area (300%) and least in the caudomedial area (10%). The existence of these lateromedial and rostrocaudal gradients was confirmed by tissue content measures of DOPAC and dopamine to DOPAC ratios in each area. The rostrocaudal gradient in the effect of uptake blockade was independent of the rostrocaudal gradient in dopamine tissue content. The regional gradients detected in dopamine uptake blockade may indicate a heterogeneous distribution in the number of uptake sites, a regional variation in the affinity of the uptake site for the blocker and/or altered neuronal activity mediated by an action of the blocker on dopaminergic cell bodies.
Glynn G E; Yamamoto B K
Brain research
1989
1989-03
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/10.1016/0006-8993(89)90799-3" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(89)90799-3</a>