Document Detail


Cocaine self-administration behaviors in ClockΔ19 mice.
MedLine Citation:
PMID:  22535308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: A key role has been identified for the circadian locomotor output cycles kaput (Clock) gene in the regulation of drug reward. Mice bearing a dominant negative mutation in the Clock gene (ClockΔ19 mice) exhibit increased cocaine-induced conditioned place preference, reduced anxiety- and depression-like behavior, increased sensitivity to intracranial self-stimulation, and increased dopaminergic cell activity in the ventral tegmental area.
OBJECTIVES: We sought to determine if this hyperhedonic phenotype extends to cocaine self-administration and measures of motivation.
METHODS: Two separate serial testing procedures were carried out (n = 7-10/genotype/schedule). Testing began with acquisition of sucrose pellet self-administration, implantation of intravenous catheter, acquisition of cocaine self-administration, and dose-response testing (fixed ratio or progressive ratio). To evaluate diurnal variations in acquisition behavior, these sessions occurred at Zeitgeber 2 (ZT2) or ZT14.
RESULTS: WT and ClockΔ19 mice exhibited similar learning and readily acquired food self-administration at both ZT2 and ZT14. However, only ClockΔ19 mice acquired cocaine self-administration at ZT2. A greater percentage of ClockΔ19 mice reached acquisition criteria at ZT2 and ZT14. ClockΔ19 mice self-administered more cocaine than WT mice. Using fixed ratio and progressive ratio schedules of reinforcement dose-response paradigms, we found that cocaine is a more efficacious reinforcer in ClockΔ19 mice than in WT mice.
CONCLUSION: Our results demonstrate that the Clock gene plays an important role in cocaine reinforcement and that decreased CLOCK function increases vulnerability for cocaine use.
Authors:
Angela Renee Ozburn; Erin Beth Larson; David W Self; Colleen A McClung
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-26
Journal Detail:
Title:  Psychopharmacology     Volume:  223     ISSN:  1432-2072     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2013-01-14     Revised Date:  2013-12-11    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  169-77     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Behavior, Animal* / drug effects
CLOCK Proteins / genetics*,  physiology
Circadian Clocks / genetics
Cocaine / administration & dosage*,  toxicity
Cocaine-Related Disorders / genetics*,  psychology
Dose-Response Relationship, Drug
Male
Mice
Mice, Inbred BALB C
Mice, Mutant Strains
Mutation*
Reinforcement (Psychology)*
Self Administration
Grant Support
ID/Acronym/Agency:
AA-020452/AA/NIAAA NIH HHS; DA-010460/DA/NIDA NIH HHS; DA-023988/DA/NIDA NIH HHS; DA-07290/DA/NIDA NIH HHS; F32 AA020452/AA/NIAAA NIH HHS; R01 DA010460/DA/NIDA NIH HHS; R01 DA023988/DA/NIDA NIH HHS; R01 DA026482/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
EC 2.3.1.48/CLOCK Proteins; EC 2.3.1.48/Clock protein, mouse; I5Y540LHVR/Cocaine
Comments/Corrections

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


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