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Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice.
MedLine Citation:
PMID:  24943644     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The repeated cycles of cessation of consumption and relapse remain the major clinical concern in treating drug addiction. The endogenous opioid system is a crucial component of the reward circuit that participates in the adaptive changes leading to relapse in the addictive processes. We have used genetically modified mice to evaluate the involvement of μ- (MOR) and δ-opioid receptor (DOR) and their main endogenous ligands, the enkephalins derived from proenkephalin (PENK) and prodynorphin (PDYN), in the reinstatement of cocaine-seeking behavior. Constitutive knockout mice of MOR, DOR, PENK and PDYN, and their wild-type littermates were trained to self-administer cocaine or to seek for palatable food, followed by a period of extinction and finally tested on a cue-induced reinstatement of seeking behavior. The four lines of knockout mice acquired operant cocaine self-administration behavior, although DOR and PENK knockout mice showed less motivation for cocaine than wild-type littermates. Moreover, cue-induced relapse was significantly decreased in MOR and DOR knockout mice. In contrast, PDYN knockout mice showed a slower extinction and increased relapse than wild-type littermates. C-Fos expression analysis revealed differential activation in brain areas related with memory and reward in these knockout mice. No differences were found in any of the four genotypes in operant responding to obtain palatable food, indicating that the changes revealed in knockout mice were not due to unspecific deficit in operant performance. Our results indicate that MOR, DOR and PDYN play a differential role in cue-induced reinstatement of cocaine-seeking behavior.Neuropsychopharmacology accepted article preview online, 19 June 2014; doi:10.1038/npp.2014.149.
Authors:
Javier Gutiérrez-Cuesta; Aurelijus Burokas; Samantha Mancino; Sami Kummer; Elena Martín-García; Rafael Maldonado
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-6-19
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  -     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-6-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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