The role of stress hormones in intentional forgetting

We can control our recollections and thoughts by trying to remember certain
experiences while trying to forget others, i.e., Intentional memory control.
Unfortunately, it appears that intentional forgetting fails exactly when this
adaptive function is of utmost importance: when we experience highly negative,
or even traumatic, events. Deficits in intentional forgetting have been
reported in stress-related psychopathology, such as post-traumatic stress
disorder (PTSD). To advance our understanding of these deficits, we first need
to understand how the healthy brain intentionally controls emotional memories
and, critically, when and why it fails under stress.

The aim of this study is to investigate the combined and independent roles of
the two major stress hormones, noradrenaline (NA) and cortisol, in intentional
forgetting under stress using a pharmacological manipulation. As such, our aim
is to administer two medicines that block the two stress hormone systems, in
order to gain insight in the mechanism underlying stress-induced impairment in
intentional forgetting. The study drugs of choice are propranolol and
metyrapone. We are not interested in the (effectiveness of) medicines
themselves, but the outcome of intentional forgetting following a
pharmacological manipulation. It is predicted that, in comparison to
propranolol and placebo, the blocking of the glucocorticoid (GC) response using
metyrapone will result in no impairment in intentional forgetting following
acute stress induction.

The study is a four-armed double-blind between-participants design.

Participants will receive either propranolol hydrochloride (40 mg oral
administration; a safe challenge that temporarily blocks * -adrenergic
receptors) or metyrapone (metopirone©, 750 mg orally administered twice, a safe
challenge that temporarily blocks cortisol synthesis) and will thereafter
experience an incidence of acute stress induction. Participants in the two
placebo conditions will experience an incidence of stress induction or a
no-stress control manipulation.

Participants will visit our facility at three time points for a screening and
one week later for two consecutive days. The screening includes the informed
consent, medical screening questionnaire and blood pressure measurement to
check for hypertension, a contraindication to propranolol.
Over both test days, participants will complete mental health questionnaires,
saliva samples (10 x sampling), a hair sample (1 sample), blood pressure
recordings (10 measurements), measures of cognitive functioning and EEG
recordings. All sampling procedures are non-invasive. The third visit will
consist of taking the study treatments (propranolol 40mg, metyrapone 2x 750mg
or placebo) and exposure to a stress manipulation or a control manipulation.
In case they experience (medical) complaints, the medical supervisor will be
contacted. The total discomfort experienced by the volunteer is minimal when
all precautions are taken into account. Most important precautions are:
determining the absence any mental or physical disorder that may interact with
propranolol or metyrapone. In addition, the stress manipulation has been shown
to be well tolerated (ECP- 77 -3- 01 - 2009 * 2).
In sum, the risk of participation is deemed negligible because both medicines
are well tolerated. If there are any side effects, these are mild and of
short-lasting nature (please also see section 5.3 and 11 in the research
protocol).