Cell-type specific expression of p11 controls cocaine reward
Margarita Arango-Lievano1, Justin T Schwarz1, Mary Vernov1
1Laboratory of Molecular Neurosurgery, Department of Neurological Surgery, Weill Cornell Medical College, New York, New York.
Biological Psychiatry
|April 15, 2014
Summary
Altering p11 protein levels in the nucleus accumbens (NAc) impacts cocaine reward. Specifically, reduced p11 in NAc neurons enhances cocaine preference, suggesting p11 as a therapeutic target for addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Addiction Research
Background:
- High comorbidity between depression and cocaine addiction suggests shared pathways.
- Nucleus accumbens (NAc) is implicated in both disorders, but cell-type specific roles are unclear.
- p11 (S100A10) downregulation in NAc causes depressive behaviors; its role in addiction is unknown.
Purpose of the Study:
- Investigate the role of p11 in the NAc in cocaine reward.
- Determine how p11 levels affect cocaine-induced behaviors and molecular changes.
- Identify specific NAc neuronal populations mediating p11's effects on cocaine reward.
Main Methods:
- Utilized mouse genetics and viral strategies to manipulate p11 levels in the NAc.
- Assessed cocaine conditioned place preference and molecular correlates.
- Examined p11 manipulation effects in distinct NAc dopaminoceptive neuronal subsets.
Main Results:
- p11 knockout mice exhibited enhanced cocaine conditioned place preference.
- Focal NAc p11 downregulation mimicked this effect; overexpression reduced preference.
- Cocaine reduced NAc p11 expression; dopamine receptor-1 (DR1) neurons mediated these effects.
Conclusions:
- Disrupted p11 homeostasis in NAc DR1 neurons contributes to cocaine's rewarding effects.
- Targeting p11 levels in the NAc offers potential therapeutic strategies for cocaine addiction.
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