Effect of cocaine and 5-HT3 receptor antagonists on 5-HT=indeced [5H]dopamine release from rat striatal synaptosomes

Yi Su-Jin, Andrew N. Gifford, Kenneth M. Johnson

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca2+-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 μM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 μM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 μM, respectively. The effect of 5-HT on Ca2+-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.

Original languageEnglish (US)
Pages (from-to)185-189
Number of pages5
JournalEuropean Journal of Pharmacology
Volume199
Issue number2
DOIs
StatePublished - Jun 25 1991

Fingerprint

Serotonin 5-HT3 Receptor Antagonists
Corpus Striatum
Receptors, Serotonin, 5-HT3
Synaptosomes
Cocaine
Dopamine
Serotonin
Tritium
Nomifensine
Ondansetron
Serotonin Receptor Agonists
Lysergic Acid Diethylamide
Inhibitory Concentration 50

Keywords

  • 5-HT receptors
  • 5-HT uptake
  • Cocaine
  • Dopamine release
  • Dopamine uptake

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effect of cocaine and 5-HT3 receptor antagonists on 5-HT=indeced [5H]dopamine release from rat striatal synaptosomes. / Su-Jin, Yi; Gifford, Andrew N.; Johnson, Kenneth M.

In: European Journal of Pharmacology, Vol. 199, No. 2, 25.06.1991, p. 185-189.

Research output: Contribution to journalArticle

Su-Jin, Yi ; Gifford, Andrew N. ; Johnson, Kenneth M. / Effect of cocaine and 5-HT3 receptor antagonists on 5-HT=indeced [5H]dopamine release from rat striatal synaptosomes. In: European Journal of Pharmacology. 1991 ; Vol. 199, No. 2. pp. 185-189.
@article{4318b5506ca74426be978ae473cce5e3,
title = "Effect of cocaine and 5-HT3 receptor antagonists on 5-HT=indeced [5H]dopamine release from rat striatal synaptosomes",
abstract = "The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca2+-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 μM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 μM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 μM, respectively. The effect of 5-HT on Ca2+-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.",
keywords = "5-HT receptors, 5-HT uptake, Cocaine, Dopamine release, Dopamine uptake",
author = "Yi Su-Jin and Gifford, {Andrew N.} and Johnson, {Kenneth M.}",
year = "1991",
month = "6",
day = "25",
doi = "10.1016/0014-2999(91)90456-Z",
language = "English (US)",
volume = "199",
pages = "185--189",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Effect of cocaine and 5-HT3 receptor antagonists on 5-HT=indeced [5H]dopamine release from rat striatal synaptosomes

AU - Su-Jin, Yi

AU - Gifford, Andrew N.

AU - Johnson, Kenneth M.

PY - 1991/6/25

Y1 - 1991/6/25

N2 - The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca2+-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 μM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 μM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 μM, respectively. The effect of 5-HT on Ca2+-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.

AB - The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca2+-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 μM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 μM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 μM, respectively. The effect of 5-HT on Ca2+-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.

KW - 5-HT receptors

KW - 5-HT uptake

KW - Cocaine

KW - Dopamine release

KW - Dopamine uptake

UR - http://www.scopus.com/inward/record.url?scp=0025831399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025831399&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(91)90456-Z

DO - 10.1016/0014-2999(91)90456-Z

M3 - Article

C2 - 1835440

AN - SCOPUS:0025831399

VL - 199

SP - 185

EP - 189

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2

ER -