Memory retrieval before or after extinction reduces recovery of fear in adolescent rats

Abstract

Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a retrieval -extinction procedure would reduce the recovery of extinguished fear in adolescent rats. Furthermore, the effect of the retrievalextinction sequence on fear recovery was examined by presenting the retrieval trial following extinction to some animals. In Experiment 1 adolescent rats received one nonreinforced CS presentation (a retrieval trial) or equivalent context exposure (no retrieval) 10 min before fear extinction. A retrieval trial shortly before extinction reduced overall levels of fear in both test contexts (i.e., it improved extinction retention and reduced renewal). In Experiment 2 a weakening of renewal was observed with a retrieval -extinction manipulation, regardless of whether the retrieval trial occurred in the training or extinction context. A key result was that a retrieval trial 10 min, but not 6 h, after extinction led to reduced overall levels of fear similar to that observed if the retrieval trial was given before extinction (Experiments 3 and 4), inconsistent with the current interpretation of the reduction in relapse being due to a disruption of reconsolidation. Together, these findings show that the impaired extinction retention observed in adolescents can be ameliorated by a very simple behavioral manipulation, but also raise some questions about the mechanisms underlying the retrieval-extinction effect.

Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit

“…These findings demonstrate that neither the animal's age at the time of fear learning or extinction determines whether fear extinction is impaired. Rather, it appears that the impairment in extinction retention previously reported in adolescence (McCallum et al 2010;Kim et al 2011;Pattwell et al 2012;Baker et al 2013) requires both fear conditioning and extinction occur in adolescence (Fig. 5).…”

“…Future studies could test whether posterior PVT activation during extinction training modulates neuronal activity in the amygdala and if lesions or inactivation of the PVT during extinction improve extinction retention in AdolesCond-Ext animals. Moreover, manipulations that either improve extinction retention, such as D-cycloserine (McCallum et al 2010), or reduce renewal of extinguished fear, such as retrieval-extinction procedures (Baker et al 2013), might reduce posterior PVT MAPK activation in adolescents.…”

“…The apparatus were similar to those used in our previous studies (see Supplemental Materials and Methods;Baker et al 2013). In brief, fear acquisition occurred in one set of chambers (Context A) while extinction and test were conducted in a second set of chambers (Context B), which had different visual features, flooring, size, and lighting to Context A.…”

Counterconditioning During Reconsolidation Prevents Relapse of Cocaine Memories

“…Nonetheless, the notion that the memory was replaced is yet to be shown Prevention of drug relapse by memory replacement K Goltseker et al directly in the future using ensemble/engram procedures (Cruz et al, 2013;Pfarr et al, 2015). Interestingly, several studies have recently shown that flipping the order of events in the retrieval-extinction procedure, that is, retrieving the memory after, rather than before extinction training, can prevent relapse in a similar manner to post-retrieval extinction (Baker et al, 2013;Millan et al, 2013), suggesting that the mechanisms underlying this procedure are not necessarily reconsolidation mechanisms. In the present study, however, flipping the order of the events, by retrieving the memory after, rather than before the counterconditioning training, did not block the reinstatement of cocaine seeking (Experiment 3b), further supporting our notion that the results we observed are mediated by memory reconsolidation mechanisms.…”

“…Thus, the memory must be retrieved to open the 'reconsolidation window', prior to any memory attenuating manipulation. However, there is evidence that a reversed protocol, in which the memory is retrieved shortly after extinction training, may also attenuate the memories and prevent the reinstatement of the target behavior (Baker et al, 2013;Millan et al, 2013). Therefore, we tested whether aversive counterconditioning followed (rather than preceded) by memory retrieval would affect the reinstatement of cocaine-seeking behavior.…”