Cocaine self-administration behaviors in ClockΔ19 mice
Open accessAbstract
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.
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Circadian genes in brain regions outside the SCN contribute locally to the control of neuronal metabolism, neurotransmitter synthesis and activity, and disruption of these functions might contribute to brain disorders.
“circadian genes in other brain regions outside of this central pace-maker also contribute locally to the control of neuronal metabolism, neurotransmitter synthesis and activity, and the disruption of these functions might contribute to brain disorders264,304–315”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [311]
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BindingDB Entry 50020610: Dopamine D
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- Authors
- Ozburn, A. R., Larson, E. B., Self, D. W., & McClung, C. A.
- Affiliations
- University of Pittsburgh (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Ozburn, Angela Renee
- Venue
- Psychopharmacology
- Published
- 2012-04-26
- Volume
- 223
- Issue
- 2
- Pages
- 169-177
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC3670183
- OpenAlex
- W1993574147
- Cited by
- 85
- References
- 32
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 9 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 10 · 2013: 3 · 2012: 2
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA020452, F32AA020452)
- National Institute on Drug Abuse (DA-010460, R01DA026482, R01DA023988, DA-07290, R29DA010460, R01DA010460, DA023988, T32DA007290)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cocaine self-administration, clock genes, circadian rhythm, cocaine reinforcement, diurnal variation, fixed-ratio schedules, progressive ratio schedule, drug reward, addiction vulnerability, locomotor activity
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Dose-Response Relationship, Drug, Male, Mice, Inbred BALB C, Mice, Mutant Strains, Mutation, Reinforcement, Psychology, Self Administration, Cocaine-Related Disorders, Mice, CLOCK Proteins, Circadian Clocks
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