Effects of Cortisol on Reconsolidation of Reactivated Fear Memories

Abstract

The return of conditioned fear after successful extinction (eg, following exposure therapy) is a significant problem in the treatment of anxiety disorders and posttraumatic stress disorder (PTSD). Targeting the reconsolidation of fear memories may allow a more lasting effect as it intervenes with the original memory trace. Indeed, several pharmacological agents and behavioral interventions have been shown to alter (enhance, impair, or otherwise update) the reconsolidation of reactivated memories of different types. Cortisol is a stress hormone and a potent modulator of learning and memory, yet its effects on fear memory reconsolidation are unclear. To investigate whether cortisol intervenes with the reconsolidation of fear memories in healthy males and how specific this effect might be, we built a 3-day reconsolidation design with skin conductance response (SCR) as a measure of conditioned fear: Fear acquisition on day 1; reactivation/no-reactivation of one conditioned stimulus and pharmacological intervention on day 2; extinction learning followed by reinstatement and reinstatement test on day 3. The groups differed only in the experimental manipulation on day 2: Reactivation+Cortisol Group, Reactivation+Placebo Group, or No-reactivation+Cortisol Group. Our results revealed an enhancing effect of cortisol on reconsolidation of the reactivated memory. The effect was highly specific, strengthening only the memory of the reactivated conditioned stimulus and not the non-reactivated one. Our findings are in line with previous findings showing an enhancing effect of behavioral stress on the reconsolidation of other types of memories. These results have implications for the understanding and treatment of anxiety disorders and PTSD.

Stress and Memory: A Selective Review on Recent Developments in the Understanding of Stress Hormone Effects on Memory and Their Clinical Relevance

“…These effects are learning‐phase dependent and are further modulated by emotional arousal and context. In addition, cortisol enhances the reconsolidation of fear memory . These findings highlight not only the potentially beneficial, but also the potentially detrimental effects of GCs within the context of treatment approaches for anxiety disorders .…”

“…With respect to fear conditioning, cortisol given during reactivation of a fear memory trace leads to a substantial and specific strengthening of the reconsolidated memory trace. This became apparent during reinstatement testing 24 h after reconsolidation manipulation . This finding might help to explain the persistence of fear memories in psychopathology.…”

Retrieval under stress decreases the long-term expression of a human declarative memory via reconsolidation

“…According to other studies, the reactivation of a declarative memory after an increase in cortisol levels, due to a stressful experience or systemic administration, leads to both retrieval deficits and long-term memory attenuation (Tollenaar, Elzinga, Spinhoven, and Everaerd, 2008a;Tollenaar et al, 2009;Tollenaar, Elzinga, Spinhoven, and Everaerd, 2008b). A recent study shows similar result when fear memories are reactivated after a stressful experience (Meir Drexler and Wolf, 2016), but see (Drexler, Merz, Hamacher-Dang, Tegenthoff, and Wolf, 2015).…”

What our eyes tell us about feelings: Tracking pupillary responses during emotion regulation processes

“…SCRs were defined as the maximum amplitude (in µS) within a window of 1–8 s after picture onset and calculated as the baseline‐to‐peak amplitude difference of the largest deflection within a window of 1–8 s after picture onset. The baseline was the skin conductance level immediately preceding the inflection point (Hamacher‐Dang, Merz, & Wolf, ; Meir Drexler, Merz, Hamacher‐Dang, Tegenthoff, & Wolf, ; Merz, Hamacher‐Dang, & Wolf, ). Data were transformed with the natural logarithm to attain a normal distribution.…”