Analysis of VMAT2 binding after methamphetamine or MPTP treatment: Disparity between homogenates and vesicle preparations

Kelly A. Hogan, Roland G.W. Staal

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

[3H]Dihydrotetrabenazine ([3H]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 [3H]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 [3H]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, [3H]DTBZ binding and active [3H]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 [3H]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.

Original languageEnglish (US)
Pages (from-to)2217-2220
Number of pages4
JournalJournal of neurochemistry
Volume74
Issue number5
DOIs
StatePublished - May 3 2000

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Methamphetamine
Dopamine
Vesicular Monoamine Transport Proteins
Tropanes
Corpus Striatum
Dopamine Plasma Membrane Transport Proteins
Synaptic Vesicles
Neurotoxins
Tyrosine 3-Monooxygenase
Ligands
Animals

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Biochemistry

Keywords

  • Dihydrotetrabenazine binding
  • Dopamine nerve terminals
  • MPTP
  • Methamphetamine
  • Striatal homogenates
  • Vesicular monoamine transporter

Cite this

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abstract = "[3H]Dihydrotetrabenazine ([3H]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 [3H]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 [3H]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, [3H]DTBZ binding and active [3H]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 [3H]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.",
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Analysis of VMAT2 binding after methamphetamine or MPTP treatment : Disparity between homogenates and vesicle preparations. / Hogan, Kelly A.; Staal, Roland G.W.

In: Journal of neurochemistry, Vol. 74, No. 5, 03.05.2000, p. 2217-2220.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of VMAT2 binding after methamphetamine or MPTP treatment

T2 - Disparity between homogenates and vesicle preparations

AU - Hogan, Kelly A.

AU - Staal, Roland G.W.

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AB - [3H]Dihydrotetrabenazine ([3H]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 [3H]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 [3H]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, [3H]DTBZ binding and active [3H]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 [3H]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.

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