1. Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behavior
- Author
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Xavier Viñals, Xavier Gallego, Mara Dierssen, Rubén D. Fernández-Montes, Rafael Maldonado, Susanna Molas, and Patricia Robledo
- Subjects
Male ,Transgene ,Nicotina ,Mice, Transgenic ,Nerve Tissue Proteins ,Motor Activity ,Receptors, Nicotinic ,Toxicology ,Impulsivity ,Developmental psychology ,Mice ,Random Allocation ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Receptor ,Pharmacology ,Genètica de la conducta ,Working memory ,Neural Inhibition ,Spontaneous alternation ,Phenotype ,Mice, Inbred C57BL ,Psychiatry and Mental health ,Nicotinic acetylcholine receptor ,Protein Subunits ,Nicotinic agonist ,Memory, Short-Term ,Gene Expression Regulation ,Impulsive Behavior ,medicine.symptom ,Psychology ,Neuroscience ,Proteïnes - Abstract
Recent studies have revealed that sequence variants in genes encoding the α3/α5/β4 nicotinic acetylcholine receptor subunits are associated with nicotine dependence. In this study, we evaluated two specific aspects of executive functioning related to drug addiction (impulsivity and working memory) in transgenic mice over expressing α3/α5/β4 nicotinic receptor subunits. Impulsivity and working memory were evaluated in an operant delayed alternation task, where mice must inhibit responding between 2 and 8s in order to receive food reinforcement. Working memory was also evaluated in a spontaneous alternation task in an open field. Transgenic mice showed less impulsive-like behavior than wild-type controls, and this behavioral phenotype was related to the number of copies of the transgene. Thus, transgenic Line 22 (16-28 copies) showed a more pronounced phenotype than Line 30 (4-5 copies). Overexpression of these subunits in Line 22 reduced spontaneous alternation behavior suggesting deficits in working memory processing in this particular paradigm. These results reveal the involvement of α3/α5/β4 nicotinic receptor subunits in working memory and impulsivity, two behavioral traits directly related to the vulnerability to develop nicotine dependence. Funding for this study was provided by the DG Research of the European Commission (PHECOMP, no. LHSM-CT-2007-037669), the Spanish ‘Instituto de Salud Carlos III’ (RD06/001/001; PI082038/nand PI10/01708, EU/FIS PS09102673, ERARare), the Spanish ‘Ministerio de Educación y Ciencia’ (SAF2007-64062; SAF2007-60827; SAF2007-31093-E; SAF2010-16427), Fundación Ramón Areces, Reina Sofia, Marató TV3, and CIBERER, The Catalan Government (SGR2009-00131; 2009SGR-1313) and the ICREA Foundation (ICREA Academia-2008)