Decrease in [3H]-serotonin binding in rat brain produced by the repeated administration of either monoamine oxidase inhibitors or centrally acting serotonin agonists

D. D. Savage, J. Mendels, Alan Frazer

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Abstract

The effect of repeated administration of monoamine oxidase inhibitors or serotonin agonists on [3H]-serotonin binding and serotonin concentrations in rat cerebral cortex was examined. Five days of clorgyline administration, which alone caused a significant reduction in [3H]-serotonin binding, was unable to do this in animals pretreated with drugs that deplete brain serotonin. Pretreatment of rats with alpha-methyl-paratyrosine did not block the clorgyline-induced reduction in [3H]-serotonin binding. Repeated treatment of rats with nialamide also lowered [3H]-serotonin binding and the return of binding sites to control values was correlated temporally with the return of the serotonin concentration to control values. Repeated administration to rats of the serotonin agonists, quipazine or TFMPP, produced a decrease in [3H]-serotonin binding. Both the clorgyline and serotonin agonist-induced reduction in [3H]-serotonin binding were due to a significant reduction in the maximum specific binding capacity with no change in the apparent binding constant. The data presented here are consistent with the hypothesis that MAO inhibitors reduce [3H]-serotonin binding indirectly, by increasing over time the exposure of serotonin receptors to the indolealkylamine.

Original languageEnglish (US)
Pages (from-to)1063-1070
Number of pages8
JournalNeuropharmacology
Volume19
Issue number11
DOIs
StatePublished - 1980
Externally publishedYes

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Serotonin Receptor Agonists
Monoamine Oxidase Inhibitors
Serotonin
Brain
Clorgyline
Nialamide
Quipazine
Serotonin Receptors
Cerebral Cortex
Binding Sites

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

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title = "Decrease in [3H]-serotonin binding in rat brain produced by the repeated administration of either monoamine oxidase inhibitors or centrally acting serotonin agonists",
abstract = "The effect of repeated administration of monoamine oxidase inhibitors or serotonin agonists on [3H]-serotonin binding and serotonin concentrations in rat cerebral cortex was examined. Five days of clorgyline administration, which alone caused a significant reduction in [3H]-serotonin binding, was unable to do this in animals pretreated with drugs that deplete brain serotonin. Pretreatment of rats with alpha-methyl-paratyrosine did not block the clorgyline-induced reduction in [3H]-serotonin binding. Repeated treatment of rats with nialamide also lowered [3H]-serotonin binding and the return of binding sites to control values was correlated temporally with the return of the serotonin concentration to control values. Repeated administration to rats of the serotonin agonists, quipazine or TFMPP, produced a decrease in [3H]-serotonin binding. Both the clorgyline and serotonin agonist-induced reduction in [3H]-serotonin binding were due to a significant reduction in the maximum specific binding capacity with no change in the apparent binding constant. The data presented here are consistent with the hypothesis that MAO inhibitors reduce [3H]-serotonin binding indirectly, by increasing over time the exposure of serotonin receptors to the indolealkylamine.",
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AU - Mendels, J.

AU - Frazer, Alan

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N2 - The effect of repeated administration of monoamine oxidase inhibitors or serotonin agonists on [3H]-serotonin binding and serotonin concentrations in rat cerebral cortex was examined. Five days of clorgyline administration, which alone caused a significant reduction in [3H]-serotonin binding, was unable to do this in animals pretreated with drugs that deplete brain serotonin. Pretreatment of rats with alpha-methyl-paratyrosine did not block the clorgyline-induced reduction in [3H]-serotonin binding. Repeated treatment of rats with nialamide also lowered [3H]-serotonin binding and the return of binding sites to control values was correlated temporally with the return of the serotonin concentration to control values. Repeated administration to rats of the serotonin agonists, quipazine or TFMPP, produced a decrease in [3H]-serotonin binding. Both the clorgyline and serotonin agonist-induced reduction in [3H]-serotonin binding were due to a significant reduction in the maximum specific binding capacity with no change in the apparent binding constant. The data presented here are consistent with the hypothesis that MAO inhibitors reduce [3H]-serotonin binding indirectly, by increasing over time the exposure of serotonin receptors to the indolealkylamine.

AB - The effect of repeated administration of monoamine oxidase inhibitors or serotonin agonists on [3H]-serotonin binding and serotonin concentrations in rat cerebral cortex was examined. Five days of clorgyline administration, which alone caused a significant reduction in [3H]-serotonin binding, was unable to do this in animals pretreated with drugs that deplete brain serotonin. Pretreatment of rats with alpha-methyl-paratyrosine did not block the clorgyline-induced reduction in [3H]-serotonin binding. Repeated treatment of rats with nialamide also lowered [3H]-serotonin binding and the return of binding sites to control values was correlated temporally with the return of the serotonin concentration to control values. Repeated administration to rats of the serotonin agonists, quipazine or TFMPP, produced a decrease in [3H]-serotonin binding. Both the clorgyline and serotonin agonist-induced reduction in [3H]-serotonin binding were due to a significant reduction in the maximum specific binding capacity with no change in the apparent binding constant. The data presented here are consistent with the hypothesis that MAO inhibitors reduce [3H]-serotonin binding indirectly, by increasing over time the exposure of serotonin receptors to the indolealkylamine.

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