This double-blind randomised trial, one of a series of trust game studies with human male subjects9, was approved by the Kyushu University Ethical Committee under the administration of the UMIN Clinical Trials Center (UMIN000004803). After a complete description of the study, all participants provided written informed consent. Either minocycline or placebo was administered to participants for 4 days, after which they participated in a trust game39.

Subjects

Participants were recruited using on-campus advertisements. Therefore, all participants were undergraduate or graduate students at Kyushu University. Healthy adult males (age range, 20–30 years) who were capable of providing informed consent were included. Participants were excluded if they met any of the following 4 criteria: (1) any history of experiencing side effects associated with antibiotics, including minocycline; (2) any history of severe heart, liver, or kidney disease; (3) a history of allergic syndromes; and (4) any history of psychiatric disorders. Their mental and physical health was confirmed via interview with a psychiatrist (TAK). After this screening process, 101 healthy adult males were enrolled in the study.

Drug administration

Participants received a hand-out describing their detailed dosing schedule. They were asked to record the exact time each dose was taken and to keep and submit all capsule packaging, as evidence of medication administration. Participants began the medication (either minocycline or placebo) on the evening of Day 1 and continued taking the medication twice daily (morning and evening) for 3 additional days. The game experiment was conducted on Day 5. Participants were instructed to take the last capsule 3 h prior to their scheduled appointment time, ensuring that all participants had similar drug levels during the actual experiment. Each capsule contained either 100 mg minocycline (in the treatment group) or 100 mg lactose (in the placebo group). This minocycline dose (200 mg/d) is within the typical range for daily dosing used to treat infections40 and has also been used in recent clinical trials4,6,14. Using a double-blind procedure in advance, participants were randomly assigned to either the treatment group or the placebo group.

Procedure

After 4 days of drug administration, participants were interviewed by a physician regarding drug side effects, other medications and adherence to the drug administration protocol. Participants then took part in the following trust game.

Trust Game with photographed female partners

In this 2-player game39, each player was initially given 1300 JPY. The first player (the male participant) then decided how much of the 1300 JPY to give to the second player (the female partner). The amount of money given to the female partner was tripled and the female partner then decided whether to split her money equally with the male participant (namely, cooperate) or to take the entire amount of money (namely, betray). The trust game structure illustrating the most extreme cases is shown in Figure 2 . All of the female partners were photographed and had decided in advance to take the entire amount of money. However, the male participants were not aware of this decision.

Figure 2 Trust Game Structure with the Most Extreme Cases. Full size image

The male participant's decision regarding how much money to give to the female partner is thought to reflect the level of trust the male participant places in his partner. The amount of money given was expected to function as a behavioural measure of the trust the male participant has in the female partner. In this experiment, male participants had no information about the female partner except for a photograph. Therefore, it is likely that male participants based their decisions regarding how much to trust each female partner, on impressions formed on the basis of the photos. After the experiment, each participant was paid an amount of money corresponding to the result of a randomly selected game from all 8 games.

Photo materials

Prior to the experiment, 61 young females were recruited using on-campus advertisements (mean age, 20.08 years; SD, 1.31 years). Each female participant was asked how they would behave in the role of the female partner in the trust game described above, especially in the case of an anonymous male participant that had chosen to give them the entire amount of money. Eleven participants answered ‘take the entire amount' rather than ‘split equally'. Eight female participants gave permission to use their photos in the experiment (mean age, 19.88 years; SD, 0.93 years). The photographs included the head and shoulders, with a neutral facial expression. During the experiment, each participant was asked if they knew each of the female partners shown in the photographs, in order to avoid confounding effects associated with previous acquaintance. However, there were no acquaintances identified among the participant pairs.

Statistical analyses

Ninety-eight Japanese males, out of 101 initially enrolled, completed all experiments (mean age, 21.49 years; SD, 1.65 years). Of the participants, 3 (1 in the minocycline condition and 2 in the placebo condition) failed to complete the experimental procedure, so the analyses were performed with data from the 98 participants. All data analyses were performed with SPSS (Version 19, IBM Corp., Armonk, NY USA).