Document Detail


Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats.
MedLine Citation:
PMID:  20394803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced changes in endocannabinoid content (piriform, prefrontal cortices), compared to group-reared rats. Our findings suggest alterations in the endocannabinoid system may contribute to the abnormal isolate phenotype. Handling modifies the endocannabinoid system and behavioral reactivity to context, but surmounts only some effects of social isolation. These data implicate a pivotal role for the endocannabinoid system in stress adaptation and emotionality-related disturbances.
Authors:
N R Sciolino; M Bortolato; S A Eisenstein; J Fu; F Oveisi; A G Hohmann; D Piomelli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-13
Journal Detail:
Title:  Neuroscience     Volume:  168     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-18     Completed Date:  2010-08-19     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  371-86     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Attention
Behavior, Animal*
Brain / metabolism
Cannabinoid Receptor Modulators / physiology*
Emotions
Endocannabinoids*
Female
Handling (Psychology)*
Male
Maze Learning
Rats
Rats, Sprague-Dawley
Receptors, Cannabinoid / metabolism
Signal Transduction
Social Isolation*
Startle Reaction
Grant Support
ID/Acronym/Agency:
DA021644S1/DA/NIDA NIH HHS; R01 DA021644/DA/NIDA NIH HHS; R01 DA021644/DA/NIDA NIH HHS; R01 DA021644-04/DA/NIDA NIH HHS; R21 DA022702/DA/NIDA NIH HHS; R21 DA022702/DA/NIDA NIH HHS; R21 DA022702-01/DA/NIDA NIH HHS; R21 DA022702-02/DA/NIDA NIH HHS; R21 DA022702-03/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Cannabinoid Receptor Modulators; 0/Endocannabinoids; 0/Receptors, Cannabinoid
Comments/Corrections
Erratum In:
Neuroscience. 2011 Jul 28;187:103

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