Document Detail

Adolescent morphine exposure affects long-term microglial function and later-life relapse liability in a model of addiction.
MedLine Citation:
PMID:  23325235     Owner:  NLM     Status:  MEDLINE    
Adolescence in humans represents a unique developmental time point associated with increased risk-taking behavior and experimentation with drugs of abuse. We hypothesized that exposure to drugs of abuse during adolescence may increase the risk of addiction in adulthood. To test this, rats were treated with a subchronic regimen of morphine or saline in adolescence, and their preference for morphine was examined using conditioned place preference (CPP) and drug-induced reinstatement in adulthood. The initial preference for morphine did not differ between groups; however, rats treated with morphine during adolescence showed robust reinstatement of morphine CPP after drug re-exposure in adulthood. This effect was not seen in rats pretreated with a subchronic regimen of morphine as adults, suggesting that exposure to morphine specifically during adolescence increases the risk of relapse to drug-seeking behavior in adulthood. We have previously established a role for microglia, the immune cells of the brain, and immune molecules in the risk of drug-induced reinstatement of morphine CPP. Thus, we examined the role of microglia within the nucleus accumbens of these rats and determined that rats exposed to morphine during adolescence had a significant increase in Toll-like receptor 4 (TLR4) mRNA and protein expression specifically on microglia. Morphine binds to TLR4 directly, and this increase in TLR4 was associated with exaggerated morphine-induced TLR4 signaling and microglial activation in rats previously exposed to morphine during adolescence. These data suggest that long-term changes in microglial function, caused by adolescent morphine exposure, alter the risk of drug-induced reinstatement in adulthood.
Jaclyn M Schwarz; Staci D Bilbo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-04-01     Revised Date:  2013-08-09    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  961-71     Citation Subset:  IM    
Department of Psychology and Neuroscience, Duke University, Durham, North Carolina 27705, USA.
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MeSH Terms
Age Factors
Conditioning, Operant / drug effects
Disease Models, Animal
Drug-Seeking Behavior
Microglia / drug effects*,  metabolism,  physiology
Minocycline / pharmacology
Morphine / pharmacology*
Narcotics / pharmacology*
Nucleus Accumbens / drug effects*,  immunology,  metabolism
Opioid-Related Disorders / immunology*,  metabolism
Pyridines / pharmacology
Rats, Sprague-Dawley
Toll-Like Receptor 4 / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Narcotics; 0/Pyridines; 0/Toll-Like Receptor 4; 10118-90-8/Minocycline; 57-27-2/Morphine; M0TTH61XC5/ibudilast

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