Document Detail


Differential effects of early environmental enrichment on emotionality related behaviours in Huntington's disease transgenic mice.
MedLine Citation:
PMID:  23045340     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Psychiatric disorders such as depression and anxiety are reported in patients with Huntington's disease (HD). Recent studies suggest beneficial effects of environmental enrichment (EE) on HD progression possibly through the serotonergic system. We investigated the potential effectiveness of EE in correcting the affective-like phenotype of female R6/1 HD mice. In addition to a behavioural battery of tests assessing depression and anxiety-related endophenotypes, we recorded physiological measures, including body temperature regulation and defecation rate as indices of stress reactivity. Finally, following identification of changes in serotonin (5-HT) receptor gene expression we measured the function of 5-HT(1A) auto- and hetero-receptors. We found that 8-week-old female HD mice exhibited higher immobility time in the forced swimming test and a decreased preference for saccharin solution. EE did not correct those depressive-like behaviours but reduced anxiety-related measures in unconditioned approach/avoidance conflict situations. Defecation rate in a large open field and change in temperature during exposure to the tail suspension test were both enhanced in HD compared to wild-type animals. Despite the enhanced hypothermic response to the 5-HT(1A) receptor agonist 8-OH-DPAT exhibited by HD mice, we found a reduction in 5-HT(1A) receptor-mediated stimulation of [(35)S]GTP-γ-S binding in the dorsal raphe nucleus and the hippocampus of HD animals. EE did not change 5-HT(1A) receptor function. Our data suggest that early EE has beneficial effects on the anxiety-like, but not on depression-like, behaviours in HD. This is the first evidence that these affective endophenotypes can be dissociated via this form of environmental stimulation. As 5-HT(1A) receptor dysfunction was not affected by EE, this receptor is unlikely to underlie the anxiety-related phenotype of HD. However, the specific regulatory role of the 5-HT(1A) autoreceptor in mediating depressive-like behaviour in HD remains to be elucidated. Interestingly, by comparing in vivo and in vitro results, our findings suggest that 8-OH-DPAT-induced hypothermia could be mediated by other targets besides the 5-HT(1A) autoreceptor, including hippocampal 5-HT(7) receptors.
Authors:
Thibault Renoir; Terence Y C Pang; Christina Mo; Grace Chan; Caroline Chevarin; Laurence Lanfumey; Anthony J Hannan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  The Journal of physiology     Volume:  591     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-06-13     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  41-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
Animals
Anxiety / physiopathology
Behavior, Animal / physiology
Depression / physiopathology
Disease Models, Animal
Emotions / physiology
Environment*
Female
Huntington Disease / physiopathology*
Hypothermia / chemically induced
Mice
Mice, Transgenic
Serotonin 5-HT1 Receptor Agonists / pharmacology
Stress, Psychological
Chemical
Reg. No./Substance:
0/Serotonin 5-HT1 Receptor Agonists; 78950-78-4/8-Hydroxy-2-(di-n-propylamino)tetralin
Comments/Corrections

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