Reinstatement of extinguished fear by an unextinguished conditional stimulus

Abstract

Anxiety disorders are often treated using extinction-based exposure therapy, but relapse is common and can occur as a result of reinstatement, whereby an aversive “trigger” can reinstate extinguished fear. Animal models of reinstatement commonly utilize a Pavlovian fear conditioning procedure, in which subjects are first trained to fear a conditional stimulus (CS) by pairing it with an aversive unconditional stimulus (US), and then extinguished by repeated presentations of the CS alone. Reinstatement is typically induced by exposing subjects to an aversive US after extinction, but here we show that exposure to a non-extinguished CS can reinstate conditional fear responding to an extinguished CS, a phenomenon we refer to as “conditional reinstatement” (CRI). Rats were trained to fear two CSs (light and tone) and subsequently underwent extinction training to only one CS (counterbalanced). Presenting the unextinguished CS (but not a novel cue) immediately after extinction reinstated conditional fear responding to the extinguished CS in a test session given 24 h later. These findings indicate that reinstatement of extinguished fear can be triggered by exposure to conditional as well as unconditional aversive stimuli, and this may help to explain why relapse is common following clinical extinction therapy in humans. Further study of CRI using animal models may prove useful for developing refined extinction therapies that are more resistant to reinstatement.

Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats

“…The ability to determine, on a subject-to-subject basis, whether remission was achieved, as well as the overall remission rate for each experimental group, is a powerful addition offered by the present analysis. A perusal of the fear conditioning/extinction literature also suggests that our fear classification criteria are very much in line with the mean data for a number of studies (the cited studies are representative examples; the list is not exhaustive) from different laboratories, in which fear extinction, and some form of return of fear were reported [9,[14][15][16][17][18][19][20]. Notably, reported means that were determined to be indicative of a significant return of fear were above 37%, and the means that were determined to indicate a significant fear reduction were below 30% (in males) [9,[14][15][16][17][18][19][20].…”

A review on human reinstatement studies: an overview and methodological challenges

“…As aversive or stressful life events affect relapse risk in anxiety related disorders (Wade et al 1993) this might be of particular clinical relevance. In support of this, a recent rodent study showed that the presentation of an unextinguished CS+ (predictive of the US during acquisition) can reinstate the CR to an extinguished CS+ (Halladay et al 2012). Earlier series of experiments (e.g., Rescorla and Heth 1975 [Exp.…”

Electric foot shock stress: a useful tool in neuropsychiatric studies

“…Thereafter, the rats are subjected to 60 extinction trials in 2 days by exposing them to conditioned stimuli alone. Subsequently, exposure to a non-extinguished conditioned stimulus reinstates the extinguished fear (Halladay et al, 2012).…”