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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Propanolol | Active Comparator | Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one Propranolol-CT 80 mg film-coated tablet. |
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| Placebo | Placebo Comparator | Memory performance for pictures, electrocortical activity, pharmacokinetics, skin-conductance, pulse waves, burdening heart frequency, pulmonary function, α-amylase in saliva, heart rate and blood pressure after administration of one placebo capsule. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| propranololhydrochloride | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| hit rate | number of correctly recognized learned pictures over number of all pictures | 90 min after study medication |
| false alarm rate | number of unlearned pictures incorrectly categorized as old over number of all pictures | 90 min after study medication |
| dicrimination index | hit rate minus false alarm rate | 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. | 90 min after study medication |
| Measure | Description | Time Frame |
|---|---|---|
| Forced Expiratory Volume in 1 second (FEV 1) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| area under the concentration time curve (AUC) of propanolol | before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication | |
| maximum concentration (Cmax) of the concentration time curve of propanolol | before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication |
Inclusion Criteria:
18 - 35 years
male
caucasian
body mass index: > 19 kg/m² and < 27 kg/m²
genotype:
good health as evidenced by the results of the clinical examination, ECG, ergometry and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state; the lower limit for systolic pressure is stated with 110 mm Hg and diastolic blood pressure with 70 mmHg as well as heart frequency should not fall below 50 bpm (WHO definition)
written informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Werner Siegmund, Prof | Department of Clinical Pharmacology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Clinical Pharmacology, Ernst-Moritz-Arndt-University Greifswald | Greifswald | Mecklenburg-Vorpommern | 17487 | Germany |
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| placebo | Drug | 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 |
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| Net Station® System and compatible Geodesic Sensor Nets® | Device | 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. |
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| VITAPORT | Device | 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. |
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| ergoselect II 100/200 | Device | 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. |
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| SpiroScout | Device | 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. |
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| Mobil-O-Graph® PWA | Device | 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. |
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| Saliva collection | Procedure | 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 |
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| up to 10 min before and 90 min and 4 h after study medication |
| heart rate | 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) | 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) | 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 | 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. | 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. | up to 10 min before and 20, 40, 60, 80, 120 min, 3, 5, 7, 11 h after study medication |
| time point of maximum concentration (tmax) of the concentration time curve (AUC) of propanolol | before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication |
| terminal half life (t1/2) of the concentration time curve of propanolol | before and 15, 30, 45, min, 1, 2, 3, 4, 6, 8, 10 and 12 h after study medication |