Abstract
The aim of the present studies was to determine the effects of reduced or absent serotonin (5-HT) transporters (5-HTTs) on 5-HT2A and 5-HT2C receptors. The density of 5-HT2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT2A mRNA was not changed in any brain region measured. 5-HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT2A receptors was evaluated by hormonal responses to (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5-HTT knockout mice. In addition, Gq and G11 proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5-HTTs changes the density of 5-HT2A and 5-HT2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of Gq/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anxiety / genetics
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Anxiety / pathology
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Autoradiography
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Brain / metabolism*
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Brain / pathology
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Carrier Proteins / genetics
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Female
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GTP-Binding Protein alpha Subunits, Gq-G11
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Heterotrimeric GTP-Binding Proteins / metabolism
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Heterozygote
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Homozygote
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In Situ Hybridization
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Indophenol / analogs & derivatives*
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Indophenol / pharmacokinetics
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Male
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Membrane Glycoproteins / deficiency*
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Membrane Glycoproteins / genetics
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Membrane Transport Proteins*
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Mice
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Mice, Knockout
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Mice, Neurologic Mutants
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Nerve Tissue Proteins*
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Organ Specificity
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RNA, Messenger / metabolism
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2C
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Receptors, Serotonin / drug effects
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Receptors, Serotonin / genetics
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Receptors, Serotonin / metabolism*
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Serotonin Antagonists / pharmacology
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Receptor Agonists / pharmacokinetics
Substances
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Carrier Proteins
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Receptor, Serotonin, 5-HT2A
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Receptor, Serotonin, 5-HT2C
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Receptors, Serotonin
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Serotonin Antagonists
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Serotonin Plasma Membrane Transport Proteins
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Serotonin Receptor Agonists
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Slc6a4 protein, mouse
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dimethoxy-4-indophenyl-2-aminopropane
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Indophenol
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GTP-Binding Protein alpha Subunits, Gq-G11
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Heterotrimeric GTP-Binding Proteins