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5-HT(1A) receptor mutant mice exhibit enhanced tonic, stress-induced and fluoxetine-induced serotonergic neurotransmission

Academic Article
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Overview

authors

  • Parsons, Loren (Larry)
  • Kerr, T. M.
  • Tecott, L. H.

publication date

  • April 2001

journal

  • Journal of Neurochemistry  Journal

abstract

  • Mutant mice that lack serotonin(1A) receptors exhibit enhanced anxiety-related behaviors, a phenotype that is hypothesized to result from impaired autoinhibitory control of midbrain serotonergic neuronal firing. Here we examined the impact of serotonin(1A) receptor deletion on forebrain serotonin neurotransmission using in vivo microdialysis in the frontal cortex and ventral hippocampus of serotonin(1A) receptor mutant and wild-type mice. Baseline dialysate serotonin levels were significantly elevated in mutant animals as compared with wild-types both in frontal cortex (mutant = 0.44 +/- 0.05 n M; wild-type = 0.28 +/- 0.03 n M) and hippocampus (mutant = 0.46 +/- 0.07 n M; wild-type = 0.27 +/- 0.04 n M). A stressor known to elicit enhanced anxiety-like behaviors in serotonin(1A) receptor mutants increased dialysate 5-HT levels in the frontal cortex of mutant mice by 144% while producing no alteration in cortical 5-HT in wild-type mice. There was no phenotypic difference in the effect of this stressor on serotonin levels in the hippocampus. Fluoxetine produced significantly greater increases in dialysate 5-HT content in serotonin(1A) receptor mutants as compared with wild-types, with two- and three-fold greater responses being observed in the hippocampus and frontal cortex, respectively. This phenotypic effect was mimicked in wild-types by pretreatment with the serotonin(1A) antagonist 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (p-MPPI). These results indicate that deletion of central serotonin(1A) receptors results in a tonic disinhibition of central serotonin neurotransmission, with a greater dysregulation of serotonin release in the frontal cortex than ventral hippocampus under conditions of stress or increased interstitial serotonin levels.

subject areas

  • Aminopyridines
  • Animals
  • Anxiety
  • Exploratory Behavior
  • Fluoxetine
  • Frontal Lobe
  • Hippocampus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Microdialysis
  • Organ Specificity
  • Phenotype
  • Piperazines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Signal Transduction
  • Stress, Psychological
  • Synaptic Transmission
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Research

keywords

  • 5-HT1AR mutant mice
  • anxiety
  • frontal cortex
  • hippocampus
  • microdialysis
  • serotonin
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Identity

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.2001.00254.x

PubMed ID

  • 11299323
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Additional Document Info

start page

  • 607

end page

  • 617

volume

  • 77

issue

  • 2

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