Pharmacological and experimental procedure
Participants were stratified for sex and randomly allocated to
treatment. Treatment was packed in identical capsules, counterbalanced
across sexes and dispensed by an independent researcher. To reduce
potential confounding effects of early life stress (46), impulsiveness,
sensitivity to punishment and reward on reward-related neural processing
the Childhood Trauma Questionnaire (CTQ), Barratt Impulsiveness Scale
(BIS), and Sensitivity to Punishment and Sensitivity to Reward
Questionnaire (SPSRQ) were administered at baseline (Figure 1A )
(47-49). Given that after oral administration LT peak plasma levels are
reached after 90 minutes with a terminal elimination half-life ranging
from 1.5 to 2.5 hours (50-52) the experimental paradigm started 90
minutes after treatment (see also(26, 53)). LT rapidly crosses the
blood-brain barrier (54, 55) and while effects at central receptors have
been observed after 30 minutes after i.e. administration effects on
cardiovascular indices only become apparent after 3 hours (e.g. (26, 29,
50)). To further control for potential confounding effects of LT on
cardiovascular activity blood pressure and heart rate were assessed
before drug administration, as well as before and after the SID fMRI
paradigm (Figure 1A , details supplementary methods ).
To control for nonspecific affective effects of LT the affective state
of participants was tracked troughout the experiment via the Spielberger
State–Trait Anxiety Inventory (STAI) and the Positive and Negative
Affective Scale (PANAS) which were administered before drug
administration, at the time of peak plasma concentrations and after the
experiment (56, 57). The subsequent affective impact of LT-induced
changes on social feedback processing was assessed via ratings of the
cues before treatment, after fMRI, and following feedback stimuli after
fMRI (Figure 1A ). After the entire experiment participants were
asked to guess the treatment they received.
Written informed consent was obtained, the study was approved by the
local institutional ethics committee, all procedure followed the
Declaration of Helsinki, and all procedures were preregistered
(NCT04604756, URL:https://clinicaltrials.gov/ct2/show/NCT04604756 ).