Selectively modulating emotional memories: Can Propranolol block reconsolidation of non-fearful, non-craving emotional memories?
Does propranolol--compared to a placebo--affect memory performance in an emotional memory task conducted in healthy adults?
Alain Brunet, PhD
36 participants
Mar 10, 2015
Interventional
Conditions
Summary
Propranolol has been used in humans to modulate emotional memories by blocking the process of memory consolidation and reconsolidation. The main emotion examined in previous studies was fear or craving. Other types of emotion have yet to be examined. Indeed, findings concerning fear-related memories may or may not extend to other types of emotional memories in humans. We elicit joy, fear, sadness, disgust and anger in healthy adults by exposing them to visual stimuli mainly drawn from the IAPS (International Affective Picture System). Using a double-blind placebo-controlled randomized study (N = 36), we test whether propranolol can block consolidation and/or reconsolidation of other forms of emotional memories.
Eligibility
Inclusion Criteria27
- a. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study;
- b. Male or female subjects aged 18 to 65 years at the time of consent;
- c. Female subjects must not be childbearing or of childbearing potential (i.e., they must be either surgically sterile, under an acceptable method of birth control, fully sexually abstinent or be one year post last menstrual period). Female subjects must meet all of the following criteria:
- Agree to avoid pregnancy during the study;
- Use one of the birth control methods listed below for the duration of the trial. Preferred methods of birth control include:
- i. An oral contraceptive agent, implantable contraceptive (e.g., Norplant) or an injectable contraceptive (e.g., Depo Provera) for at least one month prior to entering the study or prior to having sexual relations during the study and will continue its use throughout the study, or
- ii. An intrauterine device, or
- iii. Partner has had a vasectomy at least 3 months prior to study start.
- Also allowed:
- i. A latex condom
- ii. A double barrier method of a diaphragm with spermicide, plus a latex condom, or
- iii. Agree to abstain from sex for the duration of the trial;
- d. Individuals who consent to remain abstinent from all drugs of abuse (except nicotine) for 24 hours prior to enrolment;
- e. Individuals treated with the following medications must be on stable doses for at least 1-month prior to the screening visit and during the entire study: anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics;
- f. Individuals taking Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs), such as venlafaxine, must accept to skip their morning dose the day of each study visit;
- g. Individuals shall not start taking new medications on a regular basis during the study. Case-by-case decisions will be made in collaboration with the study physician regarding participants who cannot comply with this criterion;
- h. Fluency in French or English;
- f. Women who are pregnant or breast feeding;
- g. The following psychiatric conditions: Past or present bipolar disorder or psychosis;
- h. Individuals with a substance dependence or substance abuse problem;
- i. Subjects judged (based on history, mental status exam, or clinical impression, as being at significant risk of self-injurious/suicidal behaviour;
- k. Subjects having received a previous or present diagnosis of post-traumatic stress disorder (PTSD);
- l. Participation in another drug trial within 30 days prior to the screening visit or during the study;
- m. Any condition that can significantly affect the absorption of the study medication.
- n. Presence of any clinical or medical condition that might interfere with the interpretation of the efficacy and safety results.
- o. Previous exposure/familiarity to IAPS. Individuals participating in this study cannot be familiar with the IAPS as having any previous memory of the pictorial stimuli shown during the experiment could have an effect on the scientific validity of the study results.
- p. If you the participant is easily affected by emotionally stimulating images.
Exclusion Criteria4
- a. Systolic blood pressure <100 mm Hg;
- b. Cardiac rhythm below 55 beats per minute;
- c. A medical condition that contraindicates the administration of propranolol, e.g., Asthma, chronic obstructive pulmonary disease, cardiac insufficiency, second- or third-degree atrioventricular block, spastic angina, auricular sinus illness, bradycardia, Raynaud’s disease, severe peripheral vascular disease, untreated Pheochromocytoma, arterial hypotension, previous anaphylactic allergic shock;
- d. Previous adverse reaction to, or non-compliance with, beta-blocker;
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Interventions
This study will be a 3-week, randomized, double-blind trial involving a total of 36 healthy participants. Consented participants meeting enrolment criteria will be randomized with a 33% chance to one of three groups: (1) In Group A, we will give oral propranolol (tablet) at time 1 (T1) and a placebo (oral tablet) at time 2 (T2); (2) In Group B, we will give a placebo (oral tablet) at T1 and oral propranolol (tablet) at T2; (3) In Group C (control group), we will give a placebo (oral tablet) on the first two testing days. All participants will undergo a testing session once a week for a three-week period. Participants will consolidate and reconsolidate affective images drawn from the International Affective Pictorial System (IAPS) at Sessions 1 (Time 1; T1, 2 hours duration) and 2 (Time 2; T2, 1.5 hours duration), respectively, by rating each image in terms of identifying the dominant emotion and level of emotional arousal they experience while viewing each image. A memory recognition test administered at T2 and session 3 (Time 3; T3, 20 minutes durations) will serve to test for consolidation and reconsolidation of the affective images respectively. The IAPS is a collection of thousands of images tested in multiple large scale trials in order to be standardised according to arousal and valence of emotions felt. We selected a portion of these according to the type of emotion they elicit. The images range from children playing/kittens (joy) to mutilated bodies/excrement (disgust). Prior to the memory task (T1) Group A will receive an oral dose of short-acting (SA) propranolol at a dose of 1mg/kg, while the other two groups will receive a placebo. At T2, only Group B will receive SA propranolol (1mg/kg) prior to the recognition task, while the other two groups will receive a placebo. At Session 3, no medication (or placebo) will be administered to any group.
Locations(1)
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ACTRN12616000131459