Rationale Minocycline has long been applied to various infectious diseases as a tetracycline antibiotic and recently has found new application in the treatment of brain diseases such as stroke and multiple sclerosis. In addition, minocy-cline has also been suggested as an effective drug for psychiatric diseases. These suggestions imply that minocy-cline may modulate our mental activities, while the underlying mechanism remains to be clarified. Objective To investigate how minocycline influences human mental activity, we experimentally examined how minocycline works on human social decision making in a double-blind randomized trial. Methods Forty-nine healthy volunteers were administered minocycline or placebo over four days, after which they played (1) a trust game, in which they decided how much to trust an anonymous partner, and (2) a dictator game, in which they decided how to divide resources between themselves and an anonymous partner. Results The minocycline group did not display increased trusting behavior or more altruistic resource allocation. In fact, the minocycline group displayed a slight reduction in trusting behavior. However, the minocycline group did show a strong positive correlation between the degree of risk taking in the trust game and in a separate evaluation of others' trustworthiness, whereas the placebo group showed no such correlation. Conclusions These results suggest that minocycline led to more rational decision-making strategies, possibly by increasing emotion regulation. Since minocycline is a well-known inhibitor of microglial activation, our findings may open a new optional pathway for treating mental states in which a component of rational decision making is impaired.
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