Erasing Fear with Propranolol

Emotional memories last forever. Evolutionarily speaking, it is advantageous to remember the important events in life. However, some memories become harmful or maladaptive, such as in post-traumatic stress disorder, phobias, and some addictions. Psychologists and psychiatrists have tried for more than a century to erase these detrimental memories through pharmacological, psychological, and behavioral treatments, with only limited success. However, a new study published in Nature Neuroscience reports that the common medication propranolol — a member of the beta-blocker class normally used to treat hypertension — can erase the fearful element of an emotional memory.

Recently, researchers discovered that fear memories in rats are not permanent, as once thought, but change when retrieved. When a memory is retrieved, it activates new protein synthesis and alters the release of neurotransmitters in the basolateral amygdala. Propranolol can apparently disrupt this so-called “reconsolidation” of fear memories, shortly after the period of memory retrieval and reactivation, leading to a change in how the fear memory is expressed.

To investigate if the same process applied to humans, the authors of the current study induced a conditioned fearful response in 40 human volunteers. The subjects were given a mild shock when shown pictures of spiders on day 1 of the study. Their fear response was measured as the eyeblink startle reflex to a loud noise. On day 2 of the study, the memory reactivation phase, the study volunteers exhibited the same response to the fearful stimuli (the spider pictures) as on day 1. On day 3, 20 of the subjects were given 40 mg of propranolol, and the remaining 20 were given a placebo. Next, the entire group was exposed to the fearful stimuli. The propranolol group did not exhibit the same startle response as on previous days. The placebo group showed no change in startle response compared to days 1 or 2. The authors conclude that the administration of oral propranolol before reactivation of a fearful memory reduced the expression of a fearful memory and virtually eliminated the fear response.

The authors note that the propranolol did not alter the knowledge or declarative memory of the association between the stimuli and response, but this knowledge did not produce an emotional response. Propranolol acts on the beta-receptors in the amygdala during emotional information processing in humans and other animals, and may disrupt the protein synthesis that takes place during the reconsolidation of memories.

Several previous studies have reported related findings using midazolam, a short-acting benzodiazepine that reduces anxiety, and produces sedation and muscle relaxation. Benzodiazepines may also cause amnesia and impair memory. NMDA receptor antagonists have also been shown to interfere with memory reconsolidation in rats, but many of these studies have not been generalized to humans. Both of the drugs have shown variable results, depending on the age of the fearful memory and the length and number of memory reactivation sessions.

Understanding memory formation and maintenance — particularly fearful and traumatic memories — is important to the effective treatment of psychological and anxiety disorders propagated by harmful and maladaptive memories. This current study needs to be expanded and conducted on a larger scale, but may have significance for patients suffering from emotional disorders.

References

Silvia G Bustos, Héctor Maldonado, Víctor A Molina (2008). Disruptive Effect of Midazolam on Fear Memory Reconsolidation: Decisive Influence of Reactivation Time Span and Memory Age Neuropsychopharmacology, 34 (2), 446-457 DOI: 10.1038/npp.2008.75

Merel Kindt, Marieke Soeter, Bram Vervliet (2009). Beyond extinction: erasing human fear responses and preventing the return of fear Nature Neuroscience DOI: 10.1038/nn.2271

J. L. C. Lee (2006). Reconsolidation and Extinction of Conditioned Fear: Inhibition and Potentiation Journal of Neuroscience, 26 (39), 10051-10056 DOI: 10.1523/JNEUROSCI.2466-06.2006

Stephen Maren, Gregory J. Quirk (2004). Neuronal signalling of fear memory Nature Reviews Neuroscience, 5 (11), 844-852 DOI: 10.1038/nrn1535

Shirley Zhang, Jacquelyn Cranney (2008). The role of GABA and anxiety in the reconsolidation of conditioned fear. Behavioral Neuroscience, 122 (6), 1295-1305 DOI: 10.1037/a0013273