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Dominik K. E. Beyer, Lisa Horn, Nadine Klinker, Nadja Freund

• The prefrontal dopamine D1 receptor (D1R) is involved in cognitive processes. Viral overexpression of this receptor in rats further increases the reward-related behaviors and even its termination induces anhedonia and helplessness. In this study, we investigated the risky decision-making during D1R overexpression and its termination. Rats conducted the rodent version of the Iowa gambling task daily. In addition, the methyl CpG–binding protein-2 (MeCP2), one regulator connecting the dopaminergic system, cognitive processes, and mood-related behavior, was investigated after completion of the behavioral tasks. D1R overexpressing subjects exhibited maladaptive risky decision-making and risky decisions returned to control levels following termination of D1R overexpression; however, after termination, animals earned less reward compared to control subjects. In this phase, MeCP2-positive cells were elevated in the right amygdala. Our results extend the previously reported behavioral changes in the D1R-manipulated animal model to increased risk-taking and revealed differential MeCP2 expression adding further evidence for a bipolar disorder-like phenotype of this model.