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Analysis of VMAT2 Binding After Methamphetamine or MPTP Treatment
Author(s) -
Hogan Kelly A.,
Staal Roland G. W.,
Sonsalla Patricia K.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0742217.x
Subject(s) - vesicular monoamine transporter 2 , monoaminergic , neurochemical , vesicular monoamine transporter , chemistry , methamphetamine , monoamine neurotransmitter , dopamine , medicine , endocrinology , tropane , binding site , reserpine , serotonin , pharmacology , biochemistry , biology , stereochemistry , receptor
[ 3 H]Dihydrotetrabenazine ([ 3 H]DTBZ), a specific ligand for the vesicular monoamine transporter (VMAT2), has been used to characterize the integrity of monoaminergic nerve terminals in experimental animals and humans. The purpose of the present studies was to compare the loss of VMAT2 binding with the loss of other neurochemical markers of the dopamine (DA) nerve terminals in mice treated with neurotoxic doses of methamphetamine (METH) or MPTP. Profound decreases (≥70%) in DA content, tyrosine hydroxylase activity, and [ 3 H]carbomethoxy‐3‐(4‐fluorophenyl)tropane binding to the DA transporter were observed in striatal homogenates at both 1 and 6 days after exposure to the neurotoxins. It is surprising that no significant loss of [ 3 H]DTBZ binding in the homogenates was observed at 1 day after exposure, although a significant loss (‐50%) was apparent 6 days later. However, in isolated vesicle preparations, [ 3 H]DTBZ binding and active [ 3 H]DA uptake were markedly reduced (>70%) at 1 day. These observations indicate that vesicle function is compromised at an early time point after exposure to neurotoxic insult. Furthermore, the changes in [ 3 H]DTBZ binding in homogenates may not be a sensitive indicator of early damage to synaptic vesicles, although homogenate binding reliably identifies a loss of VMAT2 at later times.