Short-Term Quetiapine Treatment Alters the Use of Reinforcement Signals during Risky Decision-Making and Promotes the Choice of Negative Expected Values in Healthy Adult Males

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Effective decision-making can involve using environmental signals about the possible good and bad outcomes, and their probabilities, to select optimal actions. Problematic decision-making in psychiatric disorders, and particularly bipolar illness, may result from disrupted use of these reinforcement cues, leading to actions that reflect or precipitate pathological changes in mood. Previous experiments indicate that the processing of reinforcement cues while selecting between risky actions can be influenced by dopamine and serotonin activity. Quetiapine is an atypical antipsychotic agent with a complex pharmacology, including antagonist actions at 5-HT2A and, to a lesser extent, D2 receptors. Here, we investigated the effects of (short-term) treatment with quetiapine on the risky decision-making of healthy human adults. Twenty participants received 150 mg of quetiapine XL for 7 d, whereas 20 age- and IQ-matched participants received a placebo. On the eighth day, all participants completed a risky decision-making task that involved making a series of choices between two simultaneously presented gambles that differed in the magnitudes of their possible gains and losses, and the probabilities with which these outcomes were delivered. Quetiapine treatment was associated with a marked tendency to choose options with negative expected values compared with placebo treatment in male but not female participants. Our results demonstrate that antagonism of serotonin and dopamine receptor activity can alter the way individuals use information about gains and losses when selecting between risky actions, possibly reflecting gender-specific differences in risk attitudes. These effects may be beneficial by correcting decision-making biases that feature in mood disorders.