Journal article
Extinction Training after Cocaine Self-Administration Induces Glutamatergic Plasticity to Inhibit Cocaine Seeking
The Journal of neuroscience, Vol.30(23), pp.7984-7992
06/09/2010
DOI: 10.1523/JNEUROSCI.1244-10.2010
PMCID: PMC2893028
PMID: 20534846
Abstract
Learning to inhibit drug seeking can be an important strategy for inhibiting relapse, and this can be modeled by extinguishing drug seeking in response to a drug-paired context. Rats were either extinguished or withdrawn without extinction training (abstinence) from cocaine self-administration, and measurements of postsynaptic density proteins in the core and shell subcompartments of the nucleus accumbens were compared with yoked-saline controls. Only extinguished rats had elevations of PSD-95, Homer1b/c, and Narp in the postsynaptic density of the core, whereas no proteins measured were altered in the postsynaptic density of the shell in either extinguished or abstinent rats. Using a biotinylation strategy, it was found that surface expression of mGluR5 was reduced only in the core of extinguished animals. Although both extinguished and abstinent animals showed a reduction in long-term potentiation elicited in the core by stimulating prefrontal cortex, blunted long-term depression was observed only in extinguished rats. These data indicate that the elevation in Homer1b/c in the core may have sequestered mGluR5 away from the membrane surface and that the loss of surface mGluR5 inhibits long-term depression. Accordingly, when Homer1c was overexpressed in the core of cocaine-naive rats with an adenoassociated virus, long-term depression was inhibited. This mechanism may contribute to the inhibition of cocaine seeking by extinction training because overexpression of Homer1c in the core also inhibited cue-induced reinstatement of cocaine seeking. These data identify a cellular mechanism that may contribute to extinction-induced inhibition of cocaine seeking.
Details
- Title: Subtitle
- Extinction Training after Cocaine Self-Administration Induces Glutamatergic Plasticity to Inhibit Cocaine Seeking
- Creators
- Lori A Knackstedt - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, andKhaled Moussawi - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, andRyan Lalumiere - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, andMarek Schwendt - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, andMatthias Klugmann - Institute of Physiological Chemistry and Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55099 Mainz, GermanyPeter W Kalivas - Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.30(23), pp.7984-7992
- Publisher
- Society for Neuroscience
- DOI
- 10.1523/JNEUROSCI.1244-10.2010
- PMID
- 20534846
- PMCID
- PMC2893028
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 06/09/2010
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984070523402771
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