Accumbal 14-3-3ζ Protein Downregulation Is Associated with Cocaine-Conditioned Memory

• Published in: Neuro-Signals Vol. 19; no. 4; pp. 175 - 188
• Main Authors: Kao, Gour-Shenq, Chuang, Jia-Ying, Cherng, Chian-Fang G., Yu, Lung
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland 01.01.2011
• Subjects: 14-3-3 Proteins - metabolism; Animals; Brain - metabolism; Cocaine - metabolism; Cocaine - pharmacology; Cues; Dopamine Uptake Inhibitors - metabolism; Down-Regulation - drug effects; Electrophoresis, Gel, Two-Dimensional - methods; Memory - drug effects; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Nucleus Accumbens - metabolism; Original Paper; Nucleus accumbens; Conditioned place preference; Cocaine memory; Reinstatement; Conditioned cues
• ISSN: 1424-862X; 1424-8638
• DOI: 10.1159/000329299

Cocaine-conditioned memory has been known to cause cocaine craving and relapse, while its underlying mechanisms remain unclear. We explored accumbal protein candidates responsible for a cocaine-conditioned memory, cocaine-induced conditioned place preference (CPP). Two-dimensional gel electrophoresis in conjunction with liquid chromatography mass spectrometry analysis was utilized to identify accumbal protein candidates involved in the retrieval of cocaine-induced CPP. Among the identified candidate proteins, a downregulated 14-3-3ζ protein was chosen and confirmed by Western immunoblotting. A polymer-mediated plasmid DNA delivery system was then used to overexpress 14-3-3 protein in mouse nucleus accumbens before the CPP retrieval tests. Overexpression of accumbal 14-3-3ζ protein was found to diminish conditioned cue/context-mediated cocaine-induced CPP. In contrast, another isoform of 14-3-3 protein, 14-3-3ε protein, did not affect conditioned cue/context-mediated cocaine-induced CPP. Overexpression of accumbal 14-3-3ζ protein did not produce motor activity-impairing effect or alter local dopamine metabolism. Moreover, overexpression of accumbal 14-3-3ζ protein did not affect food-induced CPP. These results, taken together, indicated that overexpressed accumbal 14-3-3ζ protein specifically decreased conditioned cue/context-mediated cocaine memory. Further understanding of the function of accumbal 14-3-3ζ protein may shed light on the treatment of cocaine craving and relapse.