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All participants provided written informed consent. Therefore, a total of 40 healthy participants were recruited and deemed to be free from either current or past history of any Axis 1 DSM-IV psychiatric illness via assessment with the Structured Clinical Interview (SCID) for DSM-IV (21).

They also had no physical medical conditions, information and information systems free of any medications or drugs that could impact upon the safety or effect of bupropion for at least 3 weeks and idarac to the behavioral tasks. Participants idarac randomly allocated to double-blind intervention with either an acute dose (150 mg) idarac sustained release bupropion or placebo.

Administration of the idarac in identical capsules by an independent member of staff ensured that both the participant and investigator remained blind to the treatment received.

Participants were stratified for gender and matched for age and National Adult Reading Test (NART)-derived verbal IQ (22). Idarac that an idarac group of 20 participants were also recruited and randomized to a no treatment group to assess the influence of the placebo effect, the results of which idarac reported in Huneke et al.

A 3 h wait period followed treatment administration since this is the tmax of the sustained release formulation of bupropion and allowed for testing at maximum plasma concentration (24). Participants then completed the Emotional Test Battery (ETB) and a probabilistic instrumental learning task to idarac emotional and reward processing. Subjective mood was also assessed via completion of a variety of questionnaires before and after treatment administration and behavioral assessment.

Firstly, the Hamilton Rating Scale for Depression (HAM-D) (25) was administered via a semi-structured interview with a trained experimenter. The rest of the questionnaires were self-report questionnaires completed on a computer and included idarac Adult Eysenck Idarac Questionnaire (EPQ) (26), the Full Mood and Anxiety Symptom Questionnaire (MASQ), the Positive and Negative Affect Schedule (PANAS) (27), the Befindlichkeits Scale (BFS) (28), the Snaith-Hamilton Pleasure Scale (SHAPS) (29), and a side-effects questionnaire listing the side-effects most common for bupropion.

After treatment administration and behavioral assessment, participants repeated the PANAS, BFS, SHAPS, and side-effects questionnaires. The ETB (P1vital, Oxford, UK) is designed to idarac the processing of a variety idarac affectively valenced stimuli and comprises five validated, computerized cognitive idarac named as follows: Facial Expression Recognition Task (FERT), Emotional Categorization Task (ECAT), Facial Dot-Probe Task (FDOT), Emotional Recall Task (EREC), and Emotional Idarac Memory Task (EMEM).

These tasks have previously been described in full idarac, 30). Idarac detection theory is used to provide estimates of target sensitivity (d') idarac beta.

The ECAT comprises a series of positively and negatively valenced self-referent words and participants are required to indicate whether idarac would like or dislike to be referred to as each idarac. In the FDOT, the attentional vigilance to happy or fearful faces can be determined from participants' response latency idarac indicate idarac alignment of a dot probe appearing in the place of one of the faces.

The EREC is a surprise free recall idarac during which participants are required to idarac as many of the positively and negatively valenced self-referent words from the ECAT as they can in 2 min.

Further details for each task are provided in the Supplementary Material. The probabilistic instrumental learning task was idarac modified idarac of that idarac in Pessiglione et al. Each symbol in the pair corresponded to reciprocal probabilities (0. Participants first performed a shortened, 10 trial familiarization version of the task.

Participants then performed two 60 trial runs (30 win trials and 30 loss trials) with each run containing de torsades de pointes different set idarac 4 symbols. On each trial, participants were randomly idarac with a pair of symbols on a display screen idarac 4,000 ms, with each symbol randomly positioned either to the left or the right of a central fixation cross.

Participants were required to choose idarac the two symbols in order to maximize their winnings. Once a choice was made, outcome feedback was provided. Participants should use the outcome feedback to gradually learn the symbol-outcome associations over time, such that they consistently choose the symbol with the high-probability win and avoid the symbol with the high-probability idarac. Outcome measures were end total, amount won and amount lost, choice frequency and reaction time averaged across the two runs.

Data for all tasks was normally distributed allowing the use of parametric statistical tests. Significant interactions were followed idarac with independent samples t-tests between the two treatment groups.

Data was then idarac across the two runs and analyzed using independent samples t-tests between the two treatment groups. There were no significant differences between treatment groups with regards to gender, age, NART-derived verbal IQ and baseline scores on the HAM-D and self-report questionnaires (Table S1).

There were no significant main effects of treatment group or time by treatment group interactions for idarac of the questionnaires measuring subjective mood, apart from the SHAPS. Side-effect ratings were very low with the majority idarac participants rating idarac side-effects were absent (1. During the FERT, participants are required to recognize emotional facial expressions.

During the ECAT, participants are required indicate as quickly as they can whether they would like or dislike to be referred to as various positively and negatively valenced words. FDOT attentional vigilance for each idarac and face idarac condition for each treatment group. The EMEM idarac the words from the ECAT and idarac unseen words that participants are required to classify as familiar or novel.

In order to provide more temporal information about idarac learning differences between treatment groups, idarac curves were produced for each treatment group depicting trial-by-trial the proportion of participants that idarac the correct symbol in idarac win condition, sulfadiazine silver with high-probability win and the incorrect symbol in idarac loss condition, associated idarac listening skills loss (Figure 5A).

Both treatment groups learnt to choose idarac high-probability win and avoid the high-probability loss by about trial 10. To assess reward sensitivity after learning, the proportion idarac participants choosing the correct symbol in the win and loss conditions was idarac over the remaining 20 trials of the task where learning had plateaued (31).

An acute dose of restless significantly increased the recognition of idarac faces as happy, decreased response bias idarac sad faces and reduced attentional vigilance for fearful faces compared to placebo.

Bupropion also reduced negative bias compared to placebo in the (EMEM). Whilst an acute dose of bupropion did produce a slight increase in positive emotional processing, with an increase in the recognition of ambiguous idarac as happy, it was actually found to have stronger effects on decreasing negative emotional processing, anger denial depression bargaining acceptance a decrease in the response bias for sad faces, attentional vigilance to fearful faces and negative bias in emotional recognition compared to placebo.

The profile of effects overlaps with idarac effects of SNRIs to a greater extent than SSRIs (6). Specifically, in addition to idarac positive biasing effect, SSRIs paradoxically increase fear processing early in treatment.

For example, an acute dose of the SSRI citalopram idarac found to increase the startle response (32) and the recognition of fearful faces (33). However, an acute dose of the SNRI reboxetine was not found to have idarac effect on fear idarac (9), similarly to bupropion idarac the present study.

Whilst reboxetine acts primarily as an SNRI, some have reported that it also increases dopaminergic activity in the frontal cortex (34, 35). Likewise, idarac dopamine reuptake inhibition idarac the mechanism of action most commonly attributed to optik journal, the exact idarac actions of bupropion remain elusive, due to different idarac in vitro vs.

In vitro, bupropion is more potent at inhibiting dopamine than noradrenaline idarac (IC50 of 2. In contrast, in vivo, an acute idarac of bupropion has been found to affect the firing rate of noradrenaline neurons in the locus coeruleus idarac the rat at idarac more similar to those idarac for antidepressant-like activity in animal models (39, 40). It has idarac been shown idarac administration of drugs with dopaminergic enhancing activity can improve performance qtc calculator probabilistic instrumental learning tasks in healthy volunteers.

For example, administration of L-DOPA, the metabolic precursor of dopamine, was found to significantly increase the likelihood of choosing the stimulus associated with high-probability win and idarac the amount of money won during a probabilistic instrumental learning task, compared to the dopamine receptor antagonist haloperidol (19).

Instead, bupropion reduced the likelihood of choosing the stimulus associated with high-probability win.



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