title: Accumbal 14-3-3ζ protein downregulation is associated with cocaine-conditioned memory.
abstract: 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.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.
authors.forename: Gour-Shenq
authors.initials: GS
authors.lastname: Kao
authors.forename: Jia-Ying
authors.initials: JY
authors.lastname: Chuang
authors.forename: Chian-Fang G
authors.initials: CF
authors.lastname: Cherng
authors.forename: Lung
authors.initials: L
authors.lastname: Yu
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology*; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine