Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behavior.
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.
Laboratory of Neuropharmacology, Pompeu Fabra University, PRBB, Barcelona, Spain.
Xavier
X
Viñals
Susanna
S
Molas
Xavier
X
Gallego
Rubén D
RD
Fernández-Montes
Patricia
P
Robledo
Mara
M
Dierssen
Rafael
R
Maldonado
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics* / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009433:Neural Inhibition / Q000235:genetics; D021122:Protein Subunits / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D011897:Random Allocation; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000235:genetics
D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C486720:Chrnb4 protein, mouse; C523972:CHRNA5 protein, mouse