Document Detail


Treatment of depressive-like behaviour in Huntington's disease mice by chronic sertraline and exercise.
MedLine Citation:
PMID:  21718306     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Depression is the most common psychiatric disorder in Huntington's disease (HD) patients. Women are more prone to develop depression and such susceptibility might be related to 5-hydroxytryptaminergic (serotonergic) dysregulation.
EXPERIMENTAL APPROACH: We performed tests of depression-related behaviours on female R6/1 HD mice that had been chronically treated with sertraline or provided with running-wheels. Functional assessments of 5-HT(1A) and 5-HT(2A) receptors were performed by measuring behavioural and physiological responses following administration of specific agonists, in combination with analysis of hippocampal gene expression. Finally we assessed the effect of exercise on hippocampal cell proliferation.
KEY RESULTS: Female HD mice recorded increased immobility time in the forced-swimming test, reduced saccharin preference and a hyperthermic response to stress compared with wild-type animals. These alterations were improved by chronic sertraline treatment. Wheel-running also resulted in similar improvements with the exception of saccharin preference but failed to correct the hippocampal cell proliferation deficits displayed by HD mice. The benefits of sertraline treatment and exercise involved altered 5-HT(1A) autoreceptor function, as demonstrated by modulation of the exaggerated 8-OH-DPAT-induced hypothermia exhibited by female HD mice. On the other hand, sertraline treatment was unable to restore the reduced 5-HT(1A) and 5-HT(2) heteroceptor function observed in HD animals.
CONCLUSIONS AND IMPLICATIONS: We report for the first time a crucial role for 5-HT(1A) autoreceptor function in mediating the sex-specific depressive-like phenotype of female R6/1 HD mice. Our data further support a differential effect of chronic sertraline treatment and exercise on hippocampal cell proliferation despite common behavioural benefits.
Authors:
Thibault Renoir; Terence Y C Pang; Michelle S Zajac; Grace Chan; Xin Du; Leah Leang; Caroline Chevarin; Laurence Lanfumey; Anthony J Hannan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  165     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-13     Completed Date:  2012-09-07     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1375-89     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Howard Florey Institute, Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria, Australia. thibault.renoir@florey.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidepressive Agents / pharmacology*
Behavior, Animal / drug effects
Cell Proliferation / drug effects
Depressive Disorder / drug therapy,  etiology*,  therapy*
Disease Models, Animal
Female
Gene Expression / drug effects,  genetics
Hippocampus / drug effects,  metabolism
Huntington Disease / drug therapy,  psychology*,  therapy*
Mice
Mice, Transgenic
Physical Conditioning, Animal / methods*
Receptor, Serotonin, 5-HT1A / genetics,  metabolism
Receptor, Serotonin, 5-HT2A / genetics,  metabolism
Serotonin 5-HT1 Receptor Agonists / pharmacology
Serotonin 5-HT2 Receptor Agonists / pharmacology
Sertraline / pharmacology*
Swimming
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Receptor, Serotonin, 5-HT2A; 0/Serotonin 5-HT1 Receptor Agonists; 0/Serotonin 5-HT2 Receptor Agonists; 112692-38-3/Receptor, Serotonin, 5-HT1A; 79617-96-2/Sertraline
Comments/Corrections

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