Disrupting Reconsolidation of Fear Memory in Humans by a Noradrenergic β-Blocker
December 18th, 2014
Disrupting reconsolidation is a promising approach to dampen the behavioral expression of fear memory in patients with anxiety disorders or posttraumatic stress disorder. In a series of human fear conditioning studies we showed that disrupting reconsolidation by the noradrenergic β-blocker propranolol is very effective in erasing conditioned fear responding.
The overall goal of the following experiment is to permanently weaken fear, responding by targeting the process of memory reconsolidation. This is achieved by artificially installing fear in humans through differential Pavlovian conditioning. As a second step, the fear memory is retrieved, which triggers destabilization of the memory.
Next 40 milligrams of propranolol is administered in order to disrupt the process of memory reconsolidation. The results show a permanent reduction of fear based on the startle fear responding. The main advantage of this technique over existing methods like fear extinction, is that fear is permanently reduced.
The following study should be performed in a sound attenuated room attached to a separate room for the experimenter. After delivering instructions and gaining consent, obtained blood pressure and heart rate measurements following standard protocols. To begin, attach the double-sided adhesive collars to the EMG electrodes.
Use an alcohol swab to clean the participant's skin below one eye and on the forehead, instruct the participant to keep their eyes closed to avoid potential irritation. Next, fill the center of the EMG electrodes with highly conductive electrolyte gel Using a syringe, avoid introducing air bubbles within the gel that may negatively affect recordings. Attach one of the electrodes below the lower eyelid of the eye in line with the pupil in a forward gaze.
Attach the second one about 1.5 centimeters lateral to the first following the curvature of the lower eyelid. Next, attach a ground reference on the forehead. Apply a drop of conductive gel onto the shock electrodes and attach them onto the left upper wrist using a nylon Velcro strap.
Make sure the strap is not too tight. Inform the participant that the shock should be uncomfortable but not painful. Adjust the intensity of the two MS.Electric shock for each participant individually.
When ready, manually trigger the shocks. Start at an intensity of one milliamp. Continue triggering single shocks while gradually increasing the intensity in two or three milliamp increments.
Stop when the participant reports that the shock is uncomfortable but not painful. Write down the final shock level and maintain this level. Throughout the remainder of the experiment, inform the participants regarding the pictures.
Instruct them to monitor the relationship between the pictures they are seeing and the delivery of a shock. Instruct the participant to report the expectancy of an electric shock during testing. By shifting a cursor on continuous rating scales, direct the participant to keep their eyes on the screen and sit as still as possible.
Hand them headphones to wear during testing, dim the lights and shut the door. After exiting, start the experiment from the adjacent room. Begin fear acquisition by presenting 10 baseline startle probes to diminish initial startle reactivity during fear acquisition.
One of the two pictures will co terminate with the shock on a 75%reinforcement scheme, while the other picture will never be followed by the shock noise alone. Trials should be introduced during the inter trial intervals. After testing, detach the electrodes and clean them thoroughly with water.
Remove the gel completely without scratching the silver chloride layer. After cleaning, do not wipe off the water, but use a different set of electrodes on the next participant. On the second day of testing, obtain blood pressure and heart rate measurements as well as salivary samples.
Position the participant in front of the computer screen and attach the EMG and shock electrodes as shown earlier. Inform the participant that the shock level will remain the same. Inform the participant that the same two pictures will be presented on the computer screen and ask them to remember what they had learned the previous day.
Again, instruct the participants to report the expectancy of an electric shock. After dimming the lights and leaving the room, begin the memory reactivation by presenting 10 baseline startle probes to diminish initial startle reactivity. Next, present a single unreinforced CS one trial followed by a single noise alone trial.
Detach the participant from the experimental setup and let them clean off the gel. Next, guide them to a separate table to administer an oral dose of placebo pill or 40 milligrams of propranolol hydrochloride in a double-blinded manner. After dosing, begin a resting period of about 90 minutes.
Offer the participant magazines to read while waiting. Again, obtain blood pressure and heart rate measurements as well as salivary samples. After 90 minutes after collecting blood pressure and heart rate measurements, position the participant in front of the computer screen and attach the EMG and shock electrodes.
Inform the participant that the intensity of shock will remain the same. Instruct the participants that the same two pictures will be presented on the computer screen. Again, instruct the participants to report the expectancy of an electric shock during the presentation of all pictures.
Once the participant is ready, shut the door, dim the lights and start the experiment from the other room. Start the experiment by presenting 10 baseline startle probes during the extinction phase. Present about 12 unreinforced CS one and CS two trials, as well as 12 NA trials.
After extinction, present an unsigned uncondition stimulus three times for reinstatement testing. Next, present the participants with about four unreinforced CS one and CS two trials, as well as four NA trials. When testing is complete, detach the electrodes, compensate the participant and clean the electrodes thoroughly with water representative Results of US expectancy.
Ratings are shown here. Propanolol treatment does not have a significant effect on the expectancy ratings representative. Results of the startle fear responses are shown here for the placebo group.
The startle responses remained intact during testing on day three. Contrary to placebo, the administration of propranolol following retrieval eliminates the startle fear, responding at the beginning of testing on day three. Propanolol does not have any fear reducing effects when administered in the absence of memory retrieval.
After watching this video, you should have good understanding of how to artificially install and then abolish fear in humans.
Overview
This study investigates the disruption of fear memory reconsolidation using propranolol, a noradrenergic β-blocker. The findings suggest that this approach can effectively reduce conditioned fear responses in humans.
Key Study Components
Area of Science
- Neuroscience
- Psychology
- Pharmacology
Background
- Fear memories can be persistent and debilitating in anxiety disorders.
- Reconsolidation is a process where retrieved memories become unstable and can be modified.
- Propranolol has been shown to interfere with the reconsolidation of fear memories.
- This study aims to explore the effectiveness of propranolol in erasing conditioned fear responses.
Purpose of Study
- To assess the impact of propranolol on fear memory reconsolidation.
- To determine if fear responses can be permanently reduced through this method.
- To compare this technique with traditional fear extinction methods.
Methods Used
- Participants underwent differential Pavlovian conditioning to establish fear responses.
- Memory retrieval was triggered to destabilize the fear memory.
- Propranolol (40 mg) was administered to disrupt reconsolidation.
- Startle responses were measured to evaluate fear levels before and after treatment.
Main Results
- Propranolol treatment resulted in a significant reduction in fear responses.
- Participants showed decreased startle responses following propranolol administration.
- The technique demonstrated a more permanent reduction of fear compared to extinction methods.
- Results indicate the potential for pharmacological interventions in treating anxiety disorders.
Conclusions
- Disrupting reconsolidation with propranolol is effective in reducing fear memories.
- This approach may offer a new avenue for treating anxiety disorders.
- Further research is needed to explore long-term effects and applications.
