Document Detail


Sex differences in the regulation of serotonergic transmission and behavior in 5-HT receptor knockout mice.
MedLine Citation:
PMID:  15688089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Few studies have examined the relationship between genetics, stress, and sex-linked differences in neurotransmitter systems. Examining serotonin (5-HT) receptor knockout mice on stress-induced behavioral depression, female 5-HT1B receptor knockout mice demonstrated significantly reduced immobility than either male 5-HT1B receptor knockout mice or male and female wild-type mice on the tail suspension test (TST) and forced swimming test. The behavioral phenotype was identified as likely due to a disinhibition of 5-HT release, because depletion of 5-HT with parachlorophenylalanine selectively reduced immobility of female 5-HT1B receptor knockout mice in the TST. In contrast, male and female 5-HT1A receptor knockout mice demonstrated reduced immobility compared with control mice, but the depletion of 5-HT with PCPA did not reverse the antidepressant-like phenotype. Microdialysis studies confirmed significantly higher baseline levels of hippocampal 5-HT in female, but not male, 5-HT1B receptor knockout mice. Both male and female 5-HT1B receptor knockout mice demonstrated augmented dialysate responses to fluoxetine. Also, both male and female 5-HT1B receptor knockout mice demonstrated reductions of immobility in the TST after treatment with fluoxetine. Therefore, female 5-HT1B receptor knockout mice demonstrate a sex-linked disinhibition of 5-HT release that sustained higher baseline levels of hippocampal 5-HT and behavioral vulnerability to 5-HT depletion.
Authors:
Michelle D Jones; Irwin Lucki
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  30     ISSN:  0893-133X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-14     Completed Date:  2005-07-11     Revised Date:  2011-05-18    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1039-47     Citation Subset:  IM    
Affiliation:
Department of Psychiatry, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal / physiology*
Brain / anatomy & histology
Depression / psychology
Extracellular Space / drug effects,  metabolism
Female
Fenclonine / pharmacology
Fluoxetine / pharmacology
Hindlimb Suspension / physiology
Male
Mice
Mice, Knockout
Microdialysis
Motor Activity / drug effects,  genetics,  physiology
Receptor, Serotonin, 5-HT1A / drug effects,  genetics
Receptor, Serotonin, 5-HT1B / drug effects,  genetics
Receptors, Serotonin / genetics,  physiology*
Serotonin / physiology*
Serotonin Agents / pharmacology
Serotonin Uptake Inhibitors / pharmacology
Sex Characteristics
Stress, Psychological / psychology
Synaptic Transmission / physiology*
Grant Support
ID/Acronym/Agency:
MH 14654/MH/NIMH NIH HHS; MH 48125/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Receptor, Serotonin, 5-HT1B; 0/Receptors, Serotonin; 0/Serotonin Agents; 0/Serotonin Uptake Inhibitors; 112692-38-3/Receptor, Serotonin, 5-HT1A; 50-67-9/Serotonin; 54910-89-3/Fluoxetine; 7424-00-2/Fenclonine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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