Retrieval-extinction Procedure Research Articles

Memory Reconsolidation Updating in Substance Addiction: Applications, Mechanisms, and Future Prospects for Clinical Therapeutics.

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.

ABA and AAB renewal of alcohol seeking in rats are reduced by exposure to beer before extinction

Three experiments with rats examined the impact of a retrieval-extinction procedure on ABA and AAB renewal of instrumental learning. In all experiments, rats were trained to run down an alley for alcoholic beer in Context A. Then, the instrumental response underwent extinction, which was conducted in Context B for Experiments 1 and 2, and in Context A for Experiment 3. In each experiment, one group of animals received a brief exposure to the beer prior to each extinction session, whereas this beer exposure was omitted for a second group. Moreover, Experiment 2 comprised a third group that was exposed to non-alcoholic beer before each extinction session. Finally, all rats were tested in their extinction context and in a second context, which was Context A for Experiments 1 and 2, and Context B for Experiment 3. We found ABA (Experiments 1 and 2) and AAB (Experiment 3) renewal of beer seeking in those animals for which beer exposure prior to extinction was omitted. However, response recovery was not evident when animals received exposure to beer before extinction, regardless of whether alcoholic or non-alcoholic beer was used. Our results suggest that the renewal of alcohol seeking can be prevented by means of the retrieval-extinction paradigm.

RTMS effects on urges and severity of tobacco use disorder operate independently of a retrieval-extinction component and involve frontal-striatal pathways

BackgroundAlthough smoking remains a leading cause of preventable disease, the treatment options for smoking are limited. The present study evaluated the neural features underlying effects of repetitive transcranial magnetic stimulation (rTMS) for reducing smoking cravings. In addition, the efficacy of a simulated retrieval-extinction procedure to augment rTMS efficacy was examined. MethodsSixty-one individuals with tobacco use disorder (TUD) were randomized into three groups: classic rTMS, retrieval rTMS (viewed smoking videos before rTMS), and sham rTMS. rTMS was performed on the left dorsolateral prefrontal cortex (DLPFC) over 5 days using a standard figure-8 coil. Smoking cravings and brain responses to smoking cues were measured before and after rTMS treatment. Changes in functional connectivity (FC) among different brain regions were calculated. ResultsrTMS reduced smoking urges in TUD. Both active-rTMS groups demonstrated greater activations of the DLPFC, caudate, and bilateral insula relative to the sham group. Increased FC was observed between executive and reward network brain regions, and decreased FC was observed within reward network regions. Compared with standard rTMS, retrieval-extinction rTMS demonstrated similar outcomes and was associated with less activation of the medial frontal gyrus. ConclusionsrTMS increased activations in brain regions implicated in executive control and reward processing. Strengthened prefrontal–striatal pathway suggests that rTMS enhanced top-down control over smoking cravings. The retrieval–extinction process, although associated with some different and multiple similar neural correlates as the standard rTMS, did not enhance cessation outcomes.

Exposure to beer prior to extinction reduces spontaneous recovery of beer seeking in rats

In one experiment with rats, we investigated the impact of a retrieval-extinction procedure on spontaneous recovery of operant responses. Four groups of rats were trained to press a lever for beer during the first phase of the experiment. In the second phase, lever pressing underwent extinction. Each extinction session was preceded by brief exposure to the beer in two of the groups, either 15 or 120 min before each session. Then, the four groups were tested twice to measure spontaneous recovery. The first test was carried out immediately after the last extinction session for all rats. The second test took place after 60 min for one group, while for the remaining groups it was conducted after 5 days. We found spontaneous recovery in the three groups that experienced a delay of 5 days between the first and second test. However, the spontaneous recovery effect was attenuated in the group for which the reinforcer had been presented 15 min before each extinction session. Our data indicates that the retrieval-extinction paradigm may be a suitable behavioral technique for reducing the reappearance of beer-seeking behavior.

Effects of the retrieval-extinction paradigm with abstract reminders on fear memory extinction

Reactivated fear memories may enter an unstable state that could be interrupted by behavioral interventions such as the retrieval-extinction procedure. Studies of pharmacological interventions have shown that retrieval cues are not necessarily an exact reduplication of initial conditioned stimuli (CSs); they can instead be abstract word cues. However, the effectiveness of using abstract reminder cues in behavioral intervention procedures remains unknown, as do the conditions under which they are effective. The typicality of CS and the abstraction level of reminders are also likely to be important in the paradigm but have not been investigated to date. Here, in three experiments (n = 107), we manipulate the fear conditioning process, including single CS–unconditioned stimulus (US) and multiple CS–US connections, as well as the CS typicality and abstraction level of reminder cues, to explore the conditions for adopting retrieval-extinction with abstract reminders. The results of Experiments 1 and 2 show that the abstract cue is ineffective for use as a reminder in the procedure; this is the case for single exemplar category learning and perceptual discriminative learning, independent of the typicality of CS+ or the abstraction level of reminder cues. Only the outcome of Experiment 3, which contains multiple CS–US connections, shows no indication of fear return. The limitations of the study and possible interpretations of the results are discussed.

Dose-dependent effect of retrieval-extinction on preventing reinstatement of cocaine-associated memory in mice.

As a noninvasive behavioral intervention, the retrieval-extinction (R-E) procedure has drawn much research attention for its capacity to target the reconsolidation of maladaptive memories. However, later research findings suggest that the cause and consequence of R-E may be more complicated than previously suggested. For example, the R-E procedure could increase an animal's motivation for drug-seeking under certain circumstances, and the reversed extinction-retrieval (E-R) procedure could also suppress the drug memory. Two possible mechanisms underlying the R-E procedure have been proposed: the reconsolidation-update and extinction-facilitation hypotheses. To elucidate the paradoxical prior findings and examine these two hypotheses, we systematically examined the efficacy of the extinction (E), R-E, and E-R procedures in mice's low-dose versus high-dose cocaine-induced conditioned place preference (CPP) memory. We showed that the dose of cocaine is a crucial determinant of the efficacy of the three behavioral interventions. The E procedure exerted a long-lasting suppression of the low-dose cocaine CPP memory, while the R-E procedure induced more memory defects than the E and E-R procedures in its long-term suppression of the high-dose cocaine CPP memory. It warrants further investigation of whether the R-E procedure's underlying neurochemical and molecular mechanisms differ from the E and E-R procedures.

Adjunct pharmacotherapy for psychotherapy

AimsA variety of pharmacotherapies have been used to assist the psychotherapy process as “adjunctive therapies.” These drugs are used in an acute, targeted fashion, such that they are explicitly delivered in the context of psychotherapy for anxiety, mood and substance-dependence disorders (SUDs). Our narrative review highlights the potential of medically-assisted psychotherapy by outlining the current state of research on few of these medications and describing the basic science that supports their use.MethodFirstly, we researched an assortment of medications that have been used off-label to enhance psychotherapy, and selected a few that have received the most empirical attention in preclinical and clinical-trial settings. Our review of clinical trials focused on three of the most common psychiatric ailments. For all studies reviewed, we identify the strengths and weaknesses of the data supporting the use of the medications for the three aforementioned disorders.ResultD-cycloserine: accelerates the process of associative emotional learning, enhancing exposure therapy in the treatment of various anxiety disorders, including obsessive-compulsive disorder and posttraumatic stress disorder. Limited studies are available on efficacy in treating SUDs.Intranasal oxytocin: accelerates memory retrieval-extinction procedures used in posttraumatic stress disorder, and promotes prosocial cognition and behaviour, facilitating a therapeutic alliance. Sufficiently powered studies and safety studies are required before strong conclusions can be made.Propranolol: interrupts the reconsolidation of memories (leading to maladaptive learned responses) involved in posttraumatic stress disorder during memory-reactivation therapy sessions, but there is little evidence that this drug can be used for depression or SUDs.Psychedelics: may effect the brain's default mode network, engendering a transformative experience that is often followed by a reduction in psychiatric symptoms. 3,4-methylenedioxymethamphetamine may additionally modulate the amygdala response in a way that allows for reprocessing of traumatic memories, and improves the therapeutic alliance. Anxiety, mood, and SUDs appear to be positively influence by traditional and non-traditional (ketamine) psychedelics.ConclusionAlthough the efficacy of the medically-assisted psychotherapies reviewed is still under investigation, we propose that these novel treatment approaches may be preferred over traditional psychopharmacological treatments due to the presence of fewer chronic side effects, as well less toxicity and abuse potential. Furthermore, these adjunctive pharmacotherapies may help to reinforce the psychotherapeutic alliance and may ultimately yield better long-term treatment outcomes. If at least some of the adjunctive pharmacotherapies outlined in this review are found to be clinically efficacious and safe, patients will benefit from having more treatment options available to them in the future.

Retrieval-extinction as a reconsolidation-based treatment for emotional disorders:Evidence from an extinction retention test shortly after intervention

The retrieval-extinction paradigm, a non-invasive memory intervention that is methodologically similar to exposure therapy, has significant clinical application prospects for targeting memory reconsolidation. However, it is difficult to distinguish whether the effect of preventing the return of fear by retrieval-extinction depends upon the reconsolidation-based mechanism or extinction-based mechanism. This study tested extinction retention shortly after intervention to determine whether retrieval-extinction is a reconsolidation-based approach or extinction-based approach as well as exploring the effect of sleep. In our experiment, the effects on fear conditional memory of standard extinction, retrieval-extinction, and extinction-retrieval were compared using the fear test at 3 h, 12 h without a night's sleep, and 12 h with a night's sleep after the intervention. The results showed that standard extinction and extinction-retrieval procedures reduce fear 3 h after intervention, while retrieval-extinction procedure reduces fear 12 h with a night's sleep after the intervention. The results suggest that standard extinction and extinction-retrieval create an extinction memory trace that competes with original memory trace, only retrieval-extinction update the original memory trace through memory reconsolidation. These findings provide solid evidence for the reconsolidation mechanism of the retrieval-extinction paradigm and highlight the effect of sleep on memory reconsolidation.

Methadone Induced Memory Retrieval-extinction Procedure in Heroin Addicts

Methadone Induced Memory Retrieval-extinction Procedure in Heroin Addicts

Detrimental Effects of a Retrieval-Extinction Procedure on Nicotine Seeking, but Not Cocaine Seeking.

Retrieval-extinction memory reactivation procedures have been used to prevent the return of learned fear and drug seeking in preclinical models. These procedures first reactivate the original memory with a brief cue exposure (i.e., retrieval) session, and then disrupt memory reconsolidation by conducting extinction training within the reconsolidation window. The original memory is thought to be updated with the new information conveyed by extinction learning, resulting in a persistent therapeutic effect beyond that observed with extinction training alone (i.e., no retrieval). Here, we attempted to replicate the therapeutic effects on cocaine seeking reported by Xue et al. (2012), and extend these findings to nicotine seeking. Rats self-administered either cocaine or nicotine with contingent cues for weeks, and were then divided into two groups. The retrieval group underwent a 10-min retrieval session wherein drug cues were available, but drug was not. Ten minutes later, they were allowed to continue cue extinction training for an additional 60 min. The no retrieval group underwent a contiguous 70-min cue extinction session. These procedures continued for weeks, followed by a test for spontaneous recovery of drug seeking. No group differences were observed on any measure of cocaine seeking, although both groups exhibited extinction and spontaneous recovery. By contrast, for nicotine seeking, the retrieval group exhibited resistance to extinction, an effect that persisted on the spontaneous recovery test. These findings underscore the importance of drug type in the outcome of retrieval-extinction procedures and moreover indicate that retrieval-extinction procedures can be detrimental to nicotine seeking.

Basolateral amygdala is required for reconsolidation updating of heroin‐associated memory after prolonged withdrawal

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug-associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval-extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval-extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1hour before the extinction sessions decreased the heroin-priming-induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28days of withdrawal (ie, remote heroin-associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval-extinction procedure on heroin-priming-induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval-extinction procedure resembled the inhibitory effect of UCS retrieval-extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval-extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin-associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug-associated memories.

Post-retrieval Extinction Prevents Reconsolidation of Methamphetamine Memory Traces and Subsequent Reinstatement of Methamphetamine Seeking.

Methamphetamine abuse has become a serious public health problem. However, effective treatment for methamphetamine addiction remains elusive, especially considering its high rate of relapse after treatment. A conditioned stimulus (CS) memory retrieval–extinction procedure has been demonstrated to decrease reinstatement of cocaine, heroin, and alcohol seeking in rats, and to reduce cue-induced cravings in heroin and nicotine addicts. The goal of the present study is to explore the effect of the CS memory retrieval–extinction procedure on methamphetamine seeking in rats and the underlying mechanisms. We found that daily retrieval of methamphetamine-associated memories 1 h before extinction sessions decreased subsequent drug priming-induced reinstatement, spontaneous recovery, and renewal of methamphetamine seeking. We also found that retrieval of methamphetamine-associated memories induced neuronal activation in the basolateral amygdala (BLA), while presenting extinction within the time window of reconsolidation abolished the neuronal activation in BLA. These results indicate that the CS memory retrieval–extinction procedure could prevent reconsolidation of methamphetamine memory traces in BLA and subsequent methamphetamine craving and relapse.

The role of prediction error and memory destabilization in extinction of cued-fear within the reconsolidation window

Extinction of a cued-fear memory within the reconsolidation window has been proposed to prevent fear reacquisition by reconsolidation interference. This ‘retrieval-extinction’ procedure has received interest for its therapeutic potential to reduce the impact of fear memories on behavior. To fully exploit its therapeutic potential, it is critical to understand the mechanisms that underlie the ‘retrieval-extinction’ effect. If the effect depends upon reconsolidation of the original memory, then it would be predicted that destabilization, induced by prediction error, would be critical for observing the effect. Here, the dependency of the retrieval-extinction effect on memory destabilization or prediction error was investigated in pavlovian cued-fear conditioned adult male rats. The requirement for memory destabilization, and thus reconsolidation, for the retrieval-extinction effect was subsequently investigated using region-specific pharmacological blockade of dopamine D1-receptors. Intra-basolateral amygdala antagonism of dopamine D1-receptors did not prevent the reacquisition of fear associated with the retrieval-extinction procedure. The requirement for prediction error was assessed by using a reinforced or non-reinforced memory retrieval trial before extinction, compared to a no-retrieval, extinction-only control. Both the reinforced (no prediction error) and non-reinforced retrieval sessions led to a decrease in fear reacquisition, suggesting that engagement of prediction error does not influence the occurrence of retrieval-extinction. Together, these data suggest that retrieval-extinction does not require memory destabilization, since behavioral or pharmacological interventions that prevent destabilization did not disrupt any capacity to attenuate fear.

Remote fear memory is sensitive to reconditioning

Exposure of some individuals to recurring traumatic events from the same perpetrator or situation, such as during child abuse or domestic violence, is quite prevalent. Studies have shown that the number of traumatic events experienced is positively related to the severity of post-traumatic stress disorder and other mental disorders. Using a contextual fear conditioning (Cond1) and reconditioning (Cond2) paradigm, which were separated by either 1 or 35 days, we examined fear responses to immediate extinction and retrieval-extinction procedures after repeated fear conditioning stress. Based on the time interval between Cond1 and Cond2, the animals were divided into recent and remote fear memory groups. We observed that when Cond2 was performed in the original conditioning context in which Cond1 was performed, the reconditioned remote fear memory was resistant to the disruptive effect of immediate extinction and retrieval-extinction paradigms. Furthermore, the resistance to disruptive effects could be induced by very low shock intensities, which cannot even induce any fear response in naive animals. When Cond2 was performed in a novel context, animals with remote fear memory acquired a significantly higher fear response to the novel context. Our findings suggest that remote fear memory may be more sensitive to reconditioning and resistant to post-reconditioning disruption.

Human memory reconsolidation: A guiding framework and critical review of the evidence.

Research in nonhuman animals suggests that reactivation can induce a transient, unstable state in a previously consolidated memory, during which the memory can be disrupted or modified, necessitating a process of restabilization in order to persist. Such findings have sparked a wave of interest into whether this phenomenon, known as reconsolidation, occurs in humans. Translating research from animal models to human experiments and even to clinical interventions is an exciting prospect, but amid this excitement, relatively little work has critically evaluated and synthesized existing research regarding human memory reconsolidation. In this review, we formalize a framework for evaluating and designing studies aiming to demonstrate human memory reconsolidation. We use this framework to shed light on reconsolidation-based research in human procedural memory, aversive and appetitive memory, and declarative memory, covering a diverse selection of the most prominent examples of this research, including studies of memory updating, retrieval-extinction procedures, and pharmacological interventions such as propranolol. Across different types of memory and procedure, there is a wealth of observations consistent with reconsolidation. Moreover, some experimental findings are already being translated into clinically relevant interventions. However, there are a number of inconsistent findings, and the presence of alternative explanations means that we cannot conclusively infer the presence of reconsolidation at the neurobiological level from current evidence. Reconsolidation remains a viable but hotly contested explanation for some observed changes in memory expression in both humans and animals. Developing effective and efficient new reconsolidation-based treatments can be a goal that unites researchers and guides future experiments. (PsycINFO Database Record

An Additional Prior Retrieval Alters the Effects of a Retrieval-Extinction Procedure on Recent and Remote Fear Memory.

Several studies have shown that the isolated retrieval of a consolidated fear memory can induce a labile phase, during which extinction training can prevent the reinstatement, a form of relapse in which fear response to a fear-provoking context returns when a mild shock is presented. However, fear memory retrieval may also have another opposing result: the enhancement of fear memory. This implies that the fear memory trace can be modified by a brief retrieval. Unclear is whether the fear-impairing effect of retrieval-extinction (RE) is altered by a prior brief retrieval. The present study investigated the responses of recent and remote fear memories to the RE procedure after the presentation of an additional prior retrieval (priRet). We found that a single RE procedure effectively blocked the reinstatement of 2-day recent contextual fear memory. The memory-impairing effect of the RE procedure on recent fear was not observed when priRet was presented 6 or 24 h before the RE procedure. In contrast to the 2-day recent memory, the RE procedure failed to block the reinstatement of 36-day remote fear memory but successfully disrupted the return of remote fear memory after priRet. This memory-disruptive effect on remote memory did not occur when priRet was performed in a novel context. Nimodipine administration revealed that the blockade of priRet-induced processes recovered the effects of the RE procedure on both recent and remote fear memories. Our findings suggest that the susceptibility of recent and remote fear memories to RE procedures can be altered by an additional retrieval.

A preregistered, direct replication attempt of the retrieval-extinction effect in cued fear conditioning in rats

In 2009, Monfils and colleagues proposed a behavioral procedure that was said to result in a permanent attenuation of a previously established fear memory, thereby precluding a possible return of fear after extinction (Monfils, Cowansage, Klann, & LeDoux, 2009). By presenting a single retrieval trial one hour before standard extinction training, they found an enduring reduction of fear. The retrieval-extinction procedure holds great clinical potential, particularly for anxiety patients, but the findings are not undisputed, and several conceptual replications have failed to reproduce the effect. These failures have largely been attributed to small procedural differences. This preregistered study is the first endeavor to exactly replicate three key experiments of the original report by Monfils et al. (2009), thereby gauging the robustness of their seminal findings.Despite adhering to the original procedures as closely as possible, we did not find any evidence for reduced return of fear with the retrieval-extinction procedure relative to regular extinction training, as assessed through spontaneous recovery, reinstatement and renewal. Behavior of animals in the control condition (extinction only) was comparable to that in the original studies and provided an adequate baseline to reveal differences with the retrieval-extinction condition. Our null findings indicate that the effect sizes in the original paper may have been inflated and question the legitimacy of previously proposed moderators of the retrieval-extinction effect. We argue that direct experimental evaluation of purported moderators of the retrieval-extinction effect will be key to shed more light on its nature and prerequisites.

Extinction after fear memory reactivation fails to eliminate renewal in rats

Retrieving fear memories just prior to extinction has been reported to effectively erase fear memories and prevent fear relapse. The current study examined whether the type of retrieval procedure influences the ability of extinction to impair fear renewal, a form of relapse in which responding to a conditional stimulus (CS) returns outside of the extinction context. Rats first underwent Pavlovian fear conditioning with an auditory CS and footshock unconditional stimulus (US); freezing behavior served as the index of conditioned fear. Twenty-four hours later, the rats underwent a retrieval-extinction procedure. Specifically, 1h prior to extinction (45 CS-alone trials; 44 for rats receiving a CS reminder), fear memory was retrieved by either a single exposure to the CS alone, the US alone, a CS paired with the US, or exposure to the conditioning context itself. Over the next few days, conditional freezing to the extinguished CS was tested in the extinction and conditioning context in that order (i.e., an ABBA design). In the extinction context, rats that received a CS+US trial before extinction exhibited higher levels of conditional freezing than animals in all other groups, which did not differ from one another. In the renewal context, all groups showed renewal, and none of the reactivation procedures reduced renewal relative to a control group that did not receive a reactivation procedure prior to extinction. These data suggest retrieval-extinction procedures may have limited efficacy in preventing fear renewal.

A novel UCS memory retrieval-extinction procedure to inhibit relapse to drug seeking.

We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.

An isolated retrieval trial before extinction session does not prevent the return of fear

Several studies have shown that an isolated retrieval trial before the extinction session (retrieval-extinction) prevents the return of fear memory by inhibition of reconsolidation. Other studies have reported that retrieval-extinction did not prevent the return of the fear. To date, it is still unclear whether retrieval-extinction prevents the return of the original fear memory. A previous study revealed that reconsolidation of conditioned fear memory was not induced by the brevity of the retrieval session. Thus, we examined whether the number of retrievals in the retrieval-extinction paradigm was involved in the prevention of return of fear (Experiment 1). Furthermore, studies with different-age experimental subjects have shown conflicting results. We investigated the potential impact of age on the inhibitory effect of retrieval-extinction on the return of fear (Experiment 2). Our major findings were as follows: (1) Retrieval-extinction procedure did not prevent the return of fear, regardless of the intensity (number of presentations) of the stimulus inducing retrieval of fear memory. (2) The mice in both juvenile and adult age groups (4 and 8 weeks old) retrieved fear memory after retrieval-extinction. These results suggest the possibility that extinction after retrieval does not inhibit reconsolidation of previously consolidated fear memory.