Document Detail


5-HT2C receptors in the basolateral amygdala and dorsal striatum are a novel target for the anxiolytic and antidepressant effects of exercise.
MedLine Citation:
PMID:  23049953     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Physical activity reduces the incidence and severity of psychiatric disorders such as anxiety and depression. Similarly, voluntary wheel running produces anxiolytic- and antidepressant-like effects in rodent models. The specific neurobiological mechanisms underlying the beneficial properties of exercise, however, remain unclear. One relevant pharmacological target in the treatment of psychiatric disorders is the 5-HT(2C) receptor (5-HT(2C)R). Consistent with data demonstrating the anxiogenic consequences of 5-HT(2C)R activation in humans and rodents, we have previously reported that site-specific administration of the selective 5-HT(2C)R agonist CP-809101 in the lateral/basolateral amygdala (BLA) increases shock-elicited fear while administration of CP-809101 in the dorsal striatum (DS) interferes with shuttle box escape learning. These findings suggest that activation of 5-HT(2C)R in discrete brain regions contributes to specific anxiety- and depression-like behaviors and may indicate potential brain sites involved in the anxiolytic and antidepressant effects of exercise. The current studies tested the hypothesis that voluntary wheel running reduces the behavioral consequences of 5-HT(2C)R activation in the BLA and DS, specifically enhanced shock-elicited fear and interference with shuttle box escape learning. After 6 weeks of voluntary wheel running or sedentary conditions, the selective 5-HT(2C)R agonist CP-809101 was microinjected into either the BLA or the DS of adult Fischer 344 rats, and shock-elicited fear and shuttle box escape learning was assessed. Additionally, in-situ hybridization was used to determine if 6 weeks of voluntary exercise changed levels of 5-HT(2C)R mRNA. We found that voluntary wheel running reduced the behavioral effects of CP-809101 and reduced levels of 5-HT(2C)R mRNA in both the BLA and the DS. The current data indicate that expression of 5-HT(2C)R mRNA in discrete brain sites is sensitive to physical activity status of the organism, and implicates the 5-HT(2C)R as a target for the beneficial effects of physical activity on mental health.
Authors:
Benjamin N Greenwood; Paul V Strong; Alice B Loughridge; Heidi E W Day; Peter J Clark; Agnieszka Mika; Justin E Hellwinkel; Katie G Spence; Monika Fleshner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-25
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-10     Completed Date:  2013-04-10     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e46118     Citation Subset:  IM    
Affiliation:
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, USA. ben.greenwood@colorado.edu
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MeSH Terms
Descriptor/Qualifier:
Amygdala / metabolism*,  physiology
Animals
Anxiety / metabolism*
Brain / metabolism*,  physiology*
Depression / metabolism*
In Situ Hybridization
Male
Physical Conditioning, Animal / physiology*
Random Allocation
Rats
Receptor, Serotonin, 5-HT2C / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
NIMH 050479//PHS HHS; NIMH 068283//PHS HHS
Chemical
Reg. No./Substance:
0/Receptor, Serotonin, 5-HT2C
Comments/Corrections

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


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