The main objective of the present study is to combine two lines of research, investigating the interaction between emotional processing and memory performance (on both behavioral and electrophysiological levels) and its modulation by ß-blockade. Concerning pharmacological manipulations with ß-blockers, there are no studies, which investigated the effects of propranolol on electrophysiological (ERPs) and behavioral measures of recognition memory along with their codependence on individual variations of adrenergic receptors' polymorphisms. Till now, also the findings about genetic influences of ADRB1 and ADRB2 on recognition memory for emotional contents are lacking. Therefore, the current investigation has been designed to replicate the former results which revealed reduced ERP correlates of recognition memory for emotional pictures due to administration of ß-blocker propranolol. Furthermore investigators goal is to test, whether there are any differences between carriers of genetic variants of the ADRB1 and ADRB2 in memory performance and/or changes in event-related potentials and in propranolol influences on the above mentioned processes. In conclusion, investigators hypothesize: (1) a memory advantage of emotionally arousing stimuli over emotionally neutral pictures; (2) more pronounced ERP components (EPN, LPP, old-new effect) associated with encoding and memory for emotional stimuli; (3) a reduction of electrocortical correlates of emotional recognition memory (old-new effect) caused by propranolol; (4) a potential impact of genetic variants of the ADRB1 and ADRB2 on the emotional information processing and memory formation alone, and on the propranolol modulation of those processes. Furthermore, investigators hypothesize additional pharmacodynamic effects of propranolol such as influence on skin- conductance, pulse waves, burdening heart frequency, pulmonary function and metabolomics, which might depend on the ADRB1 and ADRB2 genotype.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
8
oral administration of one capsule Propanolol-CT 80 mg Filmtabletten (propranololhydrochloride, film-coated tablet encapsulated, 80 mg, single dose) together with 240 ml tap water and blood sampling at time points blank, 15, 30, 45 min, 1, 2, 3, 4, 6, 8, 10, 12 h of study days 1 and 3 and urine sampling for 24 h at study days 1 and 3 with subsequent measuring of propranolol and its clinically relevant metabolites
oral administration of one placebo capsule together with 240 ml tap water and blood sampling at time points blank, 15, 30, 45 min, 1, 2, 3, 4, 6, 8, 10, 12 h of study days 1 and 3 and urine sampling for 24 h at study days 1 and 3
Electrocortical activity will be assessed by continuous EEG recording using Net Station® System and compatible Geodesic Sensor Nets® (Electrical Geodesics Incorporated, Eugene, OR, USA), measured at days 1, 3 and 10 of the study. Event related potentials at encoding (late positive potential, LPP) and at retrieval (ERP memory old/new effect) will be computed off-line after acquisition of the data.
Measurement of the skin conductance by VITAPORT (Vitaport EDV Systeme GmbH, Erftstadt, Germany) on study days 1 and 3 at the time points before administration of the study medication, during the psychophysiological measurement and at 4 h. Furthermore, the skin conductance responses will be measured on day 10 during the psychophysiological measurement.
Performance of an ergometry by ergoselect II 100/200 (ergoline GmbH, Bitz, Germany) on study days 1 and 3 at 120 min. The burden will be the same wattage over 4 min, that corresponds to that of reaching 80% of the maximal heart frequency in the prestudy examination.
Performance of a spirometry (SpiroScout, Ganshorn Medizin Electronic GmbH, Niederlauer, Germany) with measuring of the forced expiratory volume in 1 second (FEV1) on study days 1 and 3 before administration of the study medication and at 120 min.
Measurement of pulse waves by Mobil-O-Graph® PWA (I.E.M., Stollberg, Germany) on study days 1 and 3 at the time points -10 min, 20, 40, 60, 80, 120 min, 3, 5, 7, 11 h.
Saliva collection will be performed on study days 1 and 3 at time points -10 min, 80 min, 120 min with subsequent measuring of the concentration of α -amylase
Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany
hit rate
number of correctly recognized learned pictures over number of all pictures
Time frame: 90 min after study medication
false alarm rate
number of unlearned pictures incorrectly categorized as old over number of all pictures
Time frame: 90 min after study medication
dicrimination index
hit rate minus false alarm rate
Time frame: 90 min after study medication
event-related potentials (ERPs given in µV)
ERPs were extracted from the continuous electroencephalography signal (EEG). ERPs analyzed during encoding were late positive potentials (LPPs) in the time-range 550-1000 ms after stimulus onset. ERPs analyzed during recognition were late positive complexes (LPCs) for stimuli associated with hit responses (learned pictures correctly recognized as known) and correct rejections (unlearned pictures correctly categorized as unknown) in time range 550-700 ms after stimulus onset. Subtraction of amplitude values for both types of LPCs results in ERP old/new effects.
Time frame: 90 min after study medication
Forced Expiratory Volume in 1 second (FEV 1)
Time frame: up to 10 min before and 2 h after study medication
Skin Conductance Response (SCR in the time-window up to 6.5 s after stimulus onset, in µmho)
The skin conductance will be measured between two electrodes attached to the participant's palm. SCRs will be averaged for every participant over following conditions: unpleasant, neutral and pleasant during encoding; and unpleasant old, neutral old, pleasant old, unpleasant new, neutral new, and pleasant new during recognition.
Time frame: up to 10 min before and 90 min and 4 h after study medication
heart rate
Time frame: up to 1 min before and 20, 40, 60, 80 min, 2, 3, 5, 7 and 11 h after study medication and during ergometry (0-2 min and 2-4 min) 2 h after study medication
systolic blood pressure (mmHg)
Time frame: up to 1 min before and 20, 40, 60, 80 min, 2, 3, 5, 7 and 11 h after study medication and during ergometry (0-2 min and 2-4 min) 2 h after study medication
diastolic blood pressure (mmHg)
Time frame: up to 1 min before and 20, 40, 60, 80 min, 2, 3, 5, 7 and 11 h after study medication and during ergometry (0-2 min and 2-4 min) 2 h after study medication
α-amylase activity in saliva
concentration in U/ml
Time frame: up to 1 min before and 80 min and 2 h after study medication
skin conductance level (SCL, in mikroSiemens over a time range of 120 s [µmho])
The skin conductance will be measured between two electrodes attached to the participant's palm.
Time frame: up to 10 min before and 90 min and 4 h after study medication
mean arterial pressure (MAP)
It is defined as the average arterial pressure during a single cardiac cycle.
Time frame: up to 10 min before and 20, 40, 60, 80, 120 min, 3, 5, 7, 11 h after study medication
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.