In this study, we aim to prove a double dissociation between the contribution of dopamine and norepinephrine during the acute stress response.
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the comparison of oddball performance and
performance in the cue-guided versus memory-guided attention task, between the
stress and placebo group, the stress and haloperidol group, and the stress and
propranolol group.
Secondary outcome
In this study, three secondary outcome parameters are measured. First, the
difference in vigilance and striatal-dependent cognition between the group
receiving Propranolol and the group receiving Haloperidol is investigated.
Second, the difference in neural activity between the different groups is
assessed during the oddball and visual search task.
Third, the difference in behavioral measures and neural activity in the
different groups is measured during a motivation task, a working memory task,
and an emotion task.
Background summary
A stressful event generates a cascade of bodily changes, enabling humans to
best adapt to a potential threat. A variety of disorders are tied to a
maladaptive response to a stressful event. Part of the normal stress response
entails an enhancement of the production of catecholamines in humans, notably
dopamine and norepinephrine. Although the increased production of these
neurotransmitters to stress has been documented, the function of these
catecholamines in the stress response are understudied. In this study, we
hypothesize that dopamine inhibition decreases striatal-dependent function
after acute stress, but not vigilance, while norepinephrine inhibition
decreases vigilance after acute stress, but not striatal-dependent cognition. A
better understanding of the mechanism of these catecholamines might help to
develop more effective treatment for patients with stress-related disorders.
Study objective
In this study, we aim to prove a double dissociation between the contribution
of dopamine and norepinephrine during the acute stress response.
Study design
Our hypothesis will be tested in a double-blind, placebo-controlled, between
subjects design.
Intervention
This study will investigate four groups. The first group receives the control
procedure, while groups 2,3, and four undergo the stress procedure. Group 1 and
2 additionally receive two placebos. The third group receives 2 mg of
Haloperidol as well as a placebo, while the fourth group receives 40 mg of
Propranolol as well as a placebo.
Study burden and risks
Participants will come to the lab on two different occasions. Once for
screening and a structural MRI session, and once for a functional MRI session.
During the first session, participants will perform a questionnaire battery, as
well as behavioral tasks. The days before the second session, participants are
required to refrain from drug, smoking, and alcohol use. During the second
session, participants will receive a drug or placebo. In order to make the
intake of Haloperidol and Propranolol as safe as possible, a medical screening
will be performed, and a MD will be present during the testing day. On the
testing day, participants get the drug or placebo, as well as a stress
induction test (the Socially Evaluated Cold Pressor Task). The participants
will perform some tasks before entering the MRI, in the MRI, and after the MRI
scan. Both Haloperidol and Propranolol are commonly administered, used for
clinical use, and safe in these doses (40 mg and 2 mg single use respectively).
Kapittelweg 29
Nijmegen 6525 EN
NL
Kapittelweg 29
Nijmegen 6525 EN
NL
Listed location countries
Age
Inclusion criteria
Age between 18 and 40
Right handed
BMI between 18.5 and 30
Normal or corrected to normal vision
Speaking and understanding of the English language
Exclusion criteria
Incompatibility with the MRI scanner
History of brain surgery
Possible pregnancy
Breastfeeding
Color blindness
Any relevant current or past psychiatric or psychotic disorder, including
suicidality
First degree family member with schizophrenia, bipolar disorder, or major
depressive disorder
Neurological disorder
Endocrine disorder
Endocrine treatment
Glaucoma or increased risk for glaucoma
Melanoma or undiagnosed skin lesion
Any other clinically significant hepatic, metabolic, obstructive respiratory,
renal, cerebrovascular, cardiovascular, oncological, ocular or pulmonary
disease/disorders
Raynaud*s syndrome
Hypersensitivity to Haloperidol or Propranolol
Hypertension (i.e. diastolic blood pressure >95 mmHg at rest, or systolic blood
pressure >180
mmHg at rest)
Hypotension (i.e. diastolic blood pressure <50 mmHg at rest, or systolic blood
pressure <95
mmHg at rest, or heart rate <45 bpm)
A-V block (PR interval longer than 0.20sec or irregular PR intervals)
Abnormal QTc-interval (higher than 450 for males, and 460 for females)
Frequent autonomic failure (fainting, dizziness, blurry vision)
Used prescribed medication within the last month
Use of *over the counter* medication within the last two months (excluding
paracetamol)
Dependence on alcohol or drugs
Use of alcohol within 24 hours before the test sessions
Average alcohol consumption of 3 beverages or more daily
Use of drugs within 72 hours before the test sessions
Cannabis use within 2 weeks prior to start of the study, weekly use for a
duration of at least 3
months in the last 6 months
Weekly or more use of recreational drugs or psychotropic medication
Habitual smoking (more than one pack in a week) or inability to cease smoking
for 24 hours
before testing
Irregular sleep/wake rhythm
Intense daily physical exercise
Native English speaker
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL78603.091.21 |