Alpha-synuclein deletion decreases motor impulsivity but does not affect risky decision making in a mouse Gambling Task

Rationale: There is evidence to support the role of alphasynuclein in motor impulsivity, but the extrapolation of this finding to other types of impulsivity remains to be elucidated. Objective: This study aims to investigate the role of alphasynuclein in choice impulsivity/risky decision-making bymeans of a mouse version of the Iowa Gambling Task (mIGT). Methods: Two strains of mice that differ in the expression of the alpha-synuclein gene, the C57BL/6JOlaHsd (HA) and C57BL/6J (CR), were tested in the mIGT. HA mice differ from their CR ancestors in possessing a chromosomal deletion resulting in the loss of two genes: snca, encoding alphasynuclein and mmrn1, encoding multimerin-1. Mice were trained in the mIGT until a stable pattern of responding was achieved and then the acute effects of ethanol and cocaine in choice preference were investigated. Results: No differences between the strains were evident in risky decision-making in any of the experiments, but HA mice showed consistently reduced levels of premature responding in comparison with CR mice, confirming the reduced motor impulsivity found in a previous study. Ethanol did not modify the percentage of advantageous choices in either strain, while cocaine increased the risky choice behaviour by increasing the percentage of disadvantageous choices in both strains. Conclusions: We provide further evidence for the involvement of alpha-synuclein in motor impulsivity and suggest that alpha-synuclein does not play a role in risky decision making as evaluated in the mIGT.