Serotonin uptake into dopamine neurons via dopamine transporters: A compensatory alternative

Feng Zhou, Klaus Peter Lesch, Dennis L. Murphy

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Monoamine neurons are believed to use neuronal-specific transporters to remove their own transmitters from the extracellular space and thus terminate transmission to postsynaptic neurons. We report here, for the first time, conclusive evidence that a cross clearance of serotonin into dopamine neurons exists. Such alternative uptake by different neurons is adopted under circumstances when their own transporter function is no longer adequate. When the serotonin transporter (5-HTT) is disrupted in 5-HTT knockout mice, serotonin (5-HT) is found in dopamine (DA) neurons of homozygous (-/-) but not of heterozygous (+/-) mutant mice or their normal littermates. DA neurons containing 5-HT are seen in the substantia nigra and ventral tegmental area (VTA), but not in other brain areas of 5-HTT -/- mice. Normal rats treated with a 5-HT uptake blocker paroxetine also showed similar result. To verify the role of the DA transporter in such ectopic uptake, 5-HTT -/- mice were treated with DA uptake blocker GBR-12935, ectopic 5-HT in DA neurons was disappeared. These data indicate that: (a) 5-HT can be taken into DA neurons in rats and mice when the 5-HTT is not functionally adequate to remove extracellular 5-HT; (b) the 5-HT uptake into DA neurons is not affected by the 5-HT uptake blocker paroxetine; and (c) the DA transporter is responsible for the 5-HT uptake into DA neurons. This study thus demonstrates that cross neuronal type uptake exists and serves as a compensatory backup when a specific transporter is dysfunctional. This study also demonstrates that DA neurons can store 5-HT for possible 'false neurotransmitter' or other usage.

Original languageEnglish
Pages (from-to)109-119
Number of pages11
JournalBrain Research
Volume942
Issue number1-2
DOIs
StatePublished - Jun 28 2002

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Dopaminergic Neurons
Serotonin
Paroxetine
Neurons
Serotonin Plasma Membrane Transport Proteins
Ventral Tegmental Area
Dopamine Antagonists
Extracellular Space
Substantia Nigra
Knockout Mice
Neurotransmitter Agents

Keywords

  • Dopamine transporter
  • False transmission
  • GBR-12935
  • Gene knockout
  • Paroxetine
  • Serotonin transporter
  • Transgenic mouse

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Serotonin uptake into dopamine neurons via dopamine transporters : A compensatory alternative. / Zhou, Feng; Lesch, Klaus Peter; Murphy, Dennis L.

In: Brain Research, Vol. 942, No. 1-2, 28.06.2002, p. 109-119.

Research output: Contribution to journalArticle

Zhou, Feng ; Lesch, Klaus Peter ; Murphy, Dennis L. / Serotonin uptake into dopamine neurons via dopamine transporters : A compensatory alternative. In: Brain Research. 2002 ; Vol. 942, No. 1-2. pp. 109-119.
@article{b638c1e5244246beb1c8f85d2330e022,
title = "Serotonin uptake into dopamine neurons via dopamine transporters: A compensatory alternative",
abstract = "Monoamine neurons are believed to use neuronal-specific transporters to remove their own transmitters from the extracellular space and thus terminate transmission to postsynaptic neurons. We report here, for the first time, conclusive evidence that a cross clearance of serotonin into dopamine neurons exists. Such alternative uptake by different neurons is adopted under circumstances when their own transporter function is no longer adequate. When the serotonin transporter (5-HTT) is disrupted in 5-HTT knockout mice, serotonin (5-HT) is found in dopamine (DA) neurons of homozygous (-/-) but not of heterozygous (+/-) mutant mice or their normal littermates. DA neurons containing 5-HT are seen in the substantia nigra and ventral tegmental area (VTA), but not in other brain areas of 5-HTT -/- mice. Normal rats treated with a 5-HT uptake blocker paroxetine also showed similar result. To verify the role of the DA transporter in such ectopic uptake, 5-HTT -/- mice were treated with DA uptake blocker GBR-12935, ectopic 5-HT in DA neurons was disappeared. These data indicate that: (a) 5-HT can be taken into DA neurons in rats and mice when the 5-HTT is not functionally adequate to remove extracellular 5-HT; (b) the 5-HT uptake into DA neurons is not affected by the 5-HT uptake blocker paroxetine; and (c) the DA transporter is responsible for the 5-HT uptake into DA neurons. This study thus demonstrates that cross neuronal type uptake exists and serves as a compensatory backup when a specific transporter is dysfunctional. This study also demonstrates that DA neurons can store 5-HT for possible 'false neurotransmitter' or other usage.",
keywords = "Dopamine transporter, False transmission, GBR-12935, Gene knockout, Paroxetine, Serotonin transporter, Transgenic mouse",
author = "Feng Zhou and Lesch, {Klaus Peter} and Murphy, {Dennis L.}",
year = "2002",
month = "6",
day = "28",
doi = "10.1016/S0006-8993(02)02709-9",
language = "English",
volume = "942",
pages = "109--119",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Serotonin uptake into dopamine neurons via dopamine transporters

T2 - A compensatory alternative

AU - Zhou, Feng

AU - Lesch, Klaus Peter

AU - Murphy, Dennis L.

PY - 2002/6/28

Y1 - 2002/6/28

N2 - Monoamine neurons are believed to use neuronal-specific transporters to remove their own transmitters from the extracellular space and thus terminate transmission to postsynaptic neurons. We report here, for the first time, conclusive evidence that a cross clearance of serotonin into dopamine neurons exists. Such alternative uptake by different neurons is adopted under circumstances when their own transporter function is no longer adequate. When the serotonin transporter (5-HTT) is disrupted in 5-HTT knockout mice, serotonin (5-HT) is found in dopamine (DA) neurons of homozygous (-/-) but not of heterozygous (+/-) mutant mice or their normal littermates. DA neurons containing 5-HT are seen in the substantia nigra and ventral tegmental area (VTA), but not in other brain areas of 5-HTT -/- mice. Normal rats treated with a 5-HT uptake blocker paroxetine also showed similar result. To verify the role of the DA transporter in such ectopic uptake, 5-HTT -/- mice were treated with DA uptake blocker GBR-12935, ectopic 5-HT in DA neurons was disappeared. These data indicate that: (a) 5-HT can be taken into DA neurons in rats and mice when the 5-HTT is not functionally adequate to remove extracellular 5-HT; (b) the 5-HT uptake into DA neurons is not affected by the 5-HT uptake blocker paroxetine; and (c) the DA transporter is responsible for the 5-HT uptake into DA neurons. This study thus demonstrates that cross neuronal type uptake exists and serves as a compensatory backup when a specific transporter is dysfunctional. This study also demonstrates that DA neurons can store 5-HT for possible 'false neurotransmitter' or other usage.

AB - Monoamine neurons are believed to use neuronal-specific transporters to remove their own transmitters from the extracellular space and thus terminate transmission to postsynaptic neurons. We report here, for the first time, conclusive evidence that a cross clearance of serotonin into dopamine neurons exists. Such alternative uptake by different neurons is adopted under circumstances when their own transporter function is no longer adequate. When the serotonin transporter (5-HTT) is disrupted in 5-HTT knockout mice, serotonin (5-HT) is found in dopamine (DA) neurons of homozygous (-/-) but not of heterozygous (+/-) mutant mice or their normal littermates. DA neurons containing 5-HT are seen in the substantia nigra and ventral tegmental area (VTA), but not in other brain areas of 5-HTT -/- mice. Normal rats treated with a 5-HT uptake blocker paroxetine also showed similar result. To verify the role of the DA transporter in such ectopic uptake, 5-HTT -/- mice were treated with DA uptake blocker GBR-12935, ectopic 5-HT in DA neurons was disappeared. These data indicate that: (a) 5-HT can be taken into DA neurons in rats and mice when the 5-HTT is not functionally adequate to remove extracellular 5-HT; (b) the 5-HT uptake into DA neurons is not affected by the 5-HT uptake blocker paroxetine; and (c) the DA transporter is responsible for the 5-HT uptake into DA neurons. This study thus demonstrates that cross neuronal type uptake exists and serves as a compensatory backup when a specific transporter is dysfunctional. This study also demonstrates that DA neurons can store 5-HT for possible 'false neurotransmitter' or other usage.

KW - Dopamine transporter

KW - False transmission

KW - GBR-12935

KW - Gene knockout

KW - Paroxetine

KW - Serotonin transporter

KW - Transgenic mouse

UR - http://www.scopus.com/inward/record.url?scp=0037189057&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037189057&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(02)02709-9

DO - 10.1016/S0006-8993(02)02709-9

M3 - Article

C2 - 12031859

AN - SCOPUS:0037189057

VL - 942

SP - 109

EP - 119

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -