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Psychostimulants and Vesicle Trafficking: A Novel Mechanism and Therapeutic Implications
Author(s) -
HANSON GLEN R.,
SANDOVAL VERONICA,
RIDDLE EVAN,
FLECKENSTEIN ANNETTE E.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1316.019
Subject(s) - methylphenidate , methamphetamine , vesicular monoamine transporter 2 , monoamine neurotransmitter , vesicular monoamine transporter , dopamine , pharmacology , neurodegeneration , dopamine transporter , cytosol , meth , chemistry , transporter , neuroscience , dopaminergic , medicine , biochemistry , biology , disease , enzyme , psychiatry , attention deficit hyperactivity disorder , receptor , monomer , polymer , organic chemistry , acrylate , serotonin , gene
A bstract : The monoamine vesicular transporter 2 (VMAT‐2) has been associated with dopamine (DA) sequestration and protection against neurodegeneration caused by the intracellular oxidation of this monoamine. The data presented herein suggest that methylphenidate treatment enhances the amount of VMAT‐2 protein and possibly its activity in the presynaptic cytosol, where it is able to increase the sequestration of DA and likely protect against its instability. In contrast, methamphetamine (METH) has an opposite effect on cytosolic VMAT‐2 resulting in degradation of DA terminals. The fact that posttreatment of methylphenidate after a neurotoxic regimen of METH protects against resulting loss of DA parameters suggests that treatment with methylphenidate, or other DA transporter blockers, may be protective against degenerative disorders of DA pathways, such as Parkinson's disease.