Differential effects of dopamine transporter inhibitors in the rodent Iowa Gambling Task: Relevance to mania

Abstract

Rationale: The Iowa Gambling Task (IGT) can be used to quantify impulsive and risky choice behaviors in psychiatric patients, e.g., bipolar disorder (BD) sufferers. Although developing treatments for these behaviors is important, few predictive animal models exist. Inhibition of the dopamine transporter (DAT) can model profiles of altered motor activity and exploration seen in patients with BD. The effect of DAT inhibition on impulsive choices related to BD has received limited study however. We used a rodent IGT to elucidate the effects of similarly acting drugs on risky choice behavior. Objectives: We hypothesized that (1) C57BL/6 mice could adopt the "safe" choice options in the IGT and (2) DAT inhibition would alter risk preference. Methods: Mice were trained in the IGT to a stable risk-preference and then administered the norepinephrine/DAT inhibitor amphetamine, or the more selective DAT inhibitors modafinil or GBR12909. Results: Mice developed a preference for the "safe" option, which was potentiated by amphetamine administration. GBR12909 or modafinil administration increased motor impulsivity, motivation significantly, and risk preference subtly. Conclusions: The rodent IGT can measure different impulse related behaviors and differentiate similarly acting BD-related drugs. The contrasting effects of amphetamine and modafinil in mice are similar to effects in rats and humans in corresponding IGT tasks, supporting the translational validity of the task. GBR12909 and modafinil elicited similar behaviors in the IGT, likely through a shared mechanism. Future studies using a within-session IGT are warranted to confirm the suitability of DAT inhibitors to model risk-preference in BD.

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