, 1998 and Liddle et al., 2011) as well as reward-related tasks (Wilkison et al., 1995 and Rubia et al., 2009). In this study, we investigated DAergic function in recreational users of dAMPH and healthy controls using fMRI with and without a DA challenge to determine whether dAMPH use can be linked to DAergic dysfunction in humans. We set out to answer the following questions: (1) Does striatal function differ between recreational dAMPH users and control subjects? (2) Does a DAergic challenge modulate striatal function differently in recreational dAMPH users versus control subjects? To that purpose, we investigated the response to an oral MPH challenge during

a DAergic task: anticipation of reward using a monetary incentive delay task (Knutson et al., 2001). In view of the fact that anticipation learn more of reward is linked in a large part to striatal response systems, which may be disrupted in dAMPH users, we hypothesized AZD4547 ic50 that recreational dAMPH use is associated with impaired anticipation of reward and that this abnormality is (partially) restored by increased extracellular levels of DA following oral MPH. Subjects were recruited by posting advertisements

around the medical campus, on websites and in regional newspapers. A total of eight male, recreational amphetamine users and eight male, healthy control subjects were recruited. Written informed consent was obtained from all subjects. The eligibility criterion for the Bay 11-7085 dAMPH group was previous use of dAMPH on more than 40

occasions. This threshold was chosen based on the work of Reneman et al. (2002) who found lower DAT binding in ecstasy users with average dAMPH use on more than 45 occasions. The eight control subjects were healthy subjects with no self-reported use of amphetamines. Subjects were asked to refrain from using caffeinated products on assessment days. Both controls and dAMPH users agreed to abstain from all psychoactive drugs for at least two weeks before scanning and therefore dAMPH dependence was reason for exclusion. All subjects indicated being able to abstain without external help during this two week period and were asked to comply with urine drug screening on the day they were scanned (with an enzyme-multiplied immunoassay for amphetamines, cocaine, cannabis, alcohol, opiates and benzodiazepines). Exclusion criteria for all participants were: any neuropsychiatric diagnosis or history of brain disease or injury, use of medication with affinity for DA (e.g., MPH), a positive urine-screen for any DAergic drugs or any contra-indication to MRI such as metallic implants or claustrophobia. Subjects received a small financial compensation for their participation. This study was approved by the medical ethics committee of the Academic Medical Center Amsterdam. The tasks were presented in the same order for every subject; first a go–nogo task, then the reward task and then an emotional face recognition task.