Document Detail

Age-dependent differences in dopamine transporter and vesicular monoamine transporter-2 function and their implications for methamphetamine neurotoxicity.
MedLine Citation:
PMID:  19021208     Owner:  NLM     Status:  MEDLINE    
The abuse of methamphetamine (METH) is a serious public health problem because METH can cause persistent dopaminergic deficits in the brains of both animal models and humans. Surprisingly, adolescent postnatal day (PND)40 rats are resistant to these METH-induced deficits, whereas young adult PND90 rats are not. Studies described in this report used rotating disk electrode voltammetry and western blotting techniques to investigate whether there are age-dependent differences in monoamine transporter function in PND38-42 and PND88-92 rats that could contribute to this phenomenon. The initial velocities of dopamine (DA) transport into, METH-induced DA efflux from, and DA transporter (DAT) immunoreactivity in striatal suspensions are greater in PND38-42 rats than in PND88-92 rats. DA transport velocities into vesicles that cofractionate with synaptosomal membranes after osmotic lysis are also greater in PND38-42 rats. However, there is no difference in vesicular monoamine transporter-2 (VMAT-2) immunoreactivity between the two age groups in this fraction. This suggests that younger rats have a greater capacity to sequester cytoplasmic DA into membrane-associated vesicles due to kinetically upregulated VMAT-2 and also have increased levels of functionally active DAT. In the presence of METH, these may provide additional routes of cellular efflux for DA that is released from vesicles into the cytoplasm and thereby prevent cytoplasmic DA concentrations in younger rats from rising to neurotoxic levels after drug administration. These findings provide novel insight into the age-dependent physiological regulation of neuronal DA sequestration and may advance the treatment of disorders involving abnormal DA disposition including substance abuse and Parkinson's disease.
Trent J Volz; Sarah J Farnsworth; Shane D Rowley; Glen R Hanson; Annette E Fleckenstein
Related Documents :
12527698 - In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bre...
112828 - Localization of the rat epidermal sh-protease inhibitor in the proventricular squamous ...
12003328 - Intracerebroventricular injection of glucagon-like peptide-1 decreases monoamine concen...
16934458 - Identification of isothiazole-4-carboxamidines derivatives as a novel class of alloster...
200458 - Lead potentiation of endotoxin lethality in rats: lack of effect of kininase inhibition.
23604328 - Dietary restriction augments resistance to oxidant-mediated inhibition of mitochondrial...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  63     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2008-12-17     Completed Date:  2009-03-03     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  147-51     Citation Subset:  IM    
Copyright Information:
2008 Wiley-Liss, Inc.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Age Factors
Blotting, Western
Brain / drug effects,  metabolism
Central Nervous System Stimulants / toxicity*
Dopamine / metabolism
Dopamine Plasma Membrane Transport Proteins / drug effects*,  metabolism
Methamphetamine / toxicity*
Neurons / drug effects*,  metabolism
Rats, Sprague-Dawley
Vesicular Monoamine Transport Proteins / drug effects*,  metabolism
Grant Support
DA 00378/DA/NIDA NIH HHS; DA 00869/DA/NIDA NIH HHS; DA 019447/DA/NIDA NIH HHS; DA 04222/DA/NIDA NIH HHS; DA 11389/DA/NIDA NIH HHS; DA 13367/DA/NIDA NIH HHS; K02 DA019447/DA/NIDA NIH HHS; K02 DA019447-03/DA/NIDA NIH HHS; K02 DA019447-04/DA/NIDA NIH HHS; K05 DA000378/DA/NIDA NIH HHS; K05 DA000378-06/DA/NIDA NIH HHS; K05 DA000378-07/DA/NIDA NIH HHS; K05 DA000378-08/DA/NIDA NIH HHS; P01 DA013367/DA/NIDA NIH HHS; P01 DA013367-05/DA/NIDA NIH HHS; P01 DA013367-06A2/DA/NIDA NIH HHS; R01 DA000869/DA/NIDA NIH HHS; R01 DA000869-31/DA/NIDA NIH HHS; R01 DA000869-32/DA/NIDA NIH HHS; R01 DA004222/DA/NIDA NIH HHS; R01 DA004222-21/DA/NIDA NIH HHS; R01 DA004222-22/DA/NIDA NIH HHS; R01 DA011389/DA/NIDA NIH HHS; R01 DA011389-10/DA/NIDA NIH HHS; R01 DA011389-11A1/DA/NIDA NIH HHS
Reg. No./Substance:
0/Central Nervous System Stimulants; 0/Dopamine Plasma Membrane Transport Proteins; 0/Slc18a2 protein, rat; 0/Vesicular Monoamine Transport Proteins; 44RAL3456C/Methamphetamine; VTD58H1Z2X/Dopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The potential of (-)-o-[11C]methylvesamicol for diagnosing cholinergic deficit dementia.
Next Document:  Diversity in academic medicine no. 1 case for minority faculty development today.