Selective destruction of the serotonergic fibers of the fornix-fimbria and cingulum bundle increases 5-HT1 but not 5-HT2 receptors in rat midbrain

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Abstract

Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [3H]5-HT (5-HT1 receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the Bmax in the midbrain (38%) with no change in the KD. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT1 receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [3H]spiroperidol and [3H]ketanserin to the 5-HT2 receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT1 receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT2 binding is not altered, this further supports the hypothesis that 5-HT1 and 5-HT2 receptors are distinct populations of receptors.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalEuropean Journal of Pharmacology
Volume90
Issue number4
DOIs
StatePublished - Jun 17 1983

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Brain Fornix
Serotonin 5-HT1 Receptors
Mesencephalon
Serotonin
Hippocampus
5,7-Dihydroxytryptamine
Spiperone
Ketanserin
Desipramine
Raphe Nuclei
Microinjections
Population
Hypothalamus
Ligands
Neurons
Brain

Keywords

  • 5-HT receptors
  • 5-HT receptors
  • Serotonin
  • [H]Ketanserin
  • [H]Spiroperidol

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

@article{e91de2d6bee74365b5c6af23c2963d28,
title = "Selective destruction of the serotonergic fibers of the fornix-fimbria and cingulum bundle increases 5-HT1 but not 5-HT2 receptors in rat midbrain",
abstract = "Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [3H]5-HT (5-HT1 receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the Bmax in the midbrain (38{\%}) with no change in the KD. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT1 receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [3H]spiroperidol and [3H]ketanserin to the 5-HT2 receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT1 receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT2 binding is not altered, this further supports the hypothesis that 5-HT1 and 5-HT2 receptors are distinct populations of receptors.",
keywords = "5-HT receptors, 5-HT receptors, Serotonin, [H]Ketanserin, [H]Spiroperidol",
author = "M. Quik and Efrain Azmitia",
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doi = "10.1016/0014-2999(83)90559-9",
language = "English (US)",
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pages = "377--384",
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T1 - Selective destruction of the serotonergic fibers of the fornix-fimbria and cingulum bundle increases 5-HT1 but not 5-HT2 receptors in rat midbrain

AU - Quik, M.

AU - Azmitia, Efrain

PY - 1983/6/17

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N2 - Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [3H]5-HT (5-HT1 receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the Bmax in the midbrain (38%) with no change in the KD. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT1 receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [3H]spiroperidol and [3H]ketanserin to the 5-HT2 receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT1 receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT2 binding is not altered, this further supports the hypothesis that 5-HT1 and 5-HT2 receptors are distinct populations of receptors.

AB - Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [3H]5-HT (5-HT1 receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the Bmax in the midbrain (38%) with no change in the KD. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT1 receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [3H]spiroperidol and [3H]ketanserin to the 5-HT2 receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT1 receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT2 binding is not altered, this further supports the hypothesis that 5-HT1 and 5-HT2 receptors are distinct populations of receptors.

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