Context Renewal Research Articles

The effects of a retrieval cue on renewal of conditioned responses in human appetitive conditioning

Contextual renewal of reward anticipation may be one potential mechanism underlying relapse in eating and substance use disorders. We therefore tested retrieval cues, a method derived from an inhibitory retrieval-based model of extinction learning to attenuate contextual renewal using an appetitive conditioning paradigm. A pilot study was carried out in Experiment 1 to validate a differential chocolate conditioning paradigm, in which a specific tray was set up as a conditioned stimulus (CS) for eating chocolate (unconditioned stimulus, US). Using an ABA renewal design in Experiment 2, half of the participants were presented with a retrieval cue in the acquisition phase (group AC) and the other half in the extinction phase (group EC). Presentation of the retrieval cue in the EC was associated with reduced renewal of US-expectancy, while there was a clear renewal effect for US-expectancy in the AC. One limitation was the difference in cue presentations between both groups due to the number of trials in acquisition and extinction. Experiment 3 therefore aimed at replicating the results of Experiment 2, but with fewer cue presentations for the EC to match the AC. No significant group differences were observed indicating no effect of the retrieval cue. Theoretical and clinical implications in light of the differing results are discussed.

Acute stress persistently alters instrumental motivation without affecting appetitive Pavlovian conditioning, extinction, or contextual renewal

In two experiments, we adapted the stress-enhanced fear learning approach to evaluate the persistent effects of acute stress on appetitive learning and motivation in adult male Long Evans rats. In Experiment 1, we found that exposure to a battery of footshocks in one context had no effect on the acquisition, extinction, or contextual renewal of an appetitive Pavlovian discrimination in different contexts. However, when rats were subsequently trained to respond on a progressive ratio instrumental schedule, rats with a history of shock showed lower response rates and progressive ratio break points. Extinction of the shock-associated context had little effect on progressive ratio responding. In Experiment 2, we replicated this instrumental responding deficit with a continuous reinforcement schedule when the Pavlovian phases did not intervene in the time between shock and instrumental testing. Our findings here demonstrate that highly stressful acute experiences produce long-lasting deficits in instrumental motivation for food in male rats.

Counterconditioning reduces contextual renewal in a novel context but not in the acquisition context

As extinction is a context-dependent form of learning, conditioned responses tend to return when the conditioned stimulus (CS) is encountered outside the extinction context, known as contextual renewal. Counterconditioning is a technique that may lead to a more persistent reduction of the conditioned response. However, the effects of aversive-to-appetitive counterconditioning on contextual renewal in rodent studies are mixed. Further, research in humans is sparse, particularly direct statistical comparisons between counterconditioning and standard extinction techniques within the same study. Using a causal associative learning framework (the allergist task) implemented online, we compared the effectiveness of counterconditioning to standard extinction in preventing the renewal of judgements on the allergic properties of different food items (CSs). In a between-subjects design, 328 participants first learned that particular food items (CSs) lead to an allergic reaction in a specific restaurant (context A). Next, one CS was extinguished (no allergic reaction) while another CS was counterconditioned (positive outcome) in restaurant B. Causal judgements of the allergic properties of food items occurred in either the response acquisition context (ABA group, N = 112), the response reduction context where extinction and counterconditioning had occurred (ABB group, N = 107), or a novel context (ABC group, N = 109). Results showed that counterconditioning, compared to extinction, diminished the renewal of causal judgements to the CS in a novel context (ABC group). Still, casual judgements returned for both counter-conditioned and extinguished CSs in the response acquisition context (ABA group). Counterconditioning and extinction were similarly effective at preventing recovery of causal judgements in the response reduction context (ABB group); however, only in context B did participants choose the counter-conditioned CS as less likely to cause an allergic reaction in comparison to the extinguished CS. These findings indicate scenarios in which counterconditioning is more effective than standard extinction at diminishing the return of threat associations, with implications for improving the generalization of safety learning.

Guided reactivation of personal phobic memories prior to exposure exercises prevents the renewal of fear responses in subjects with claustrophobic fears

Background and objectivesBasic research suggest behavioral strategies for interferencing the reconsolidation of fear memories to be a promising approach in reducing clinical fears. However, first clinical studies revealed mixed results highlighting the need to identify boundary conditions. We experimentally tested the specific hypothesis that post-retrieval threat exposure prevents context renewal usually observed in protocols without fear memory reactivation. MethodsIn a preliminary investigation forty-three individuals with claustrophobic fears reactivated the individual phobic memory or not during a guided emotional imagery task and then performed standardized threat exposure to provide new information for updating the original memory. During retests seven and 28 days later, the context was different from that during treatment in half of the subjects. ResultsIn those who were guided, the fear memory was successfully reactivated as indexed by increased skin conductance level (SCL) during the imagery of personal scenes relative to neutral scenes. During retests the subjects of the memory non-activation group showed a return of reported fear after context change that, however, was not observed after post-retrieval exposure. In line, autonomic arousal (SCL) decreased over time in the memory reactivation group only if the context changed during retest. LimitationsLimited sample size and the inclusion of an analog sample reduce the generalizability of the results. ConclusionsThe reactivation of fear memory prior to treatment through guided imagery of past personal phobic situations prevented contextual renewal of phobic fears which was observed in those subjects without reactivation of memory.

Effects of a cue associated with cocaine or food reinforcers on extinction and postextinction return of behavior.

Studies of instrumental responding often include the delivery of a cue that is coincident with the delivery of the reinforcer. One purpose of this is for the cue to be removed during extinction and then presented later to assess whether responding returns (cue-induced reinstatement). In two experiments, we examined the effects of having a cue associated with reinforcement present or absent during extinction. In Experiment 1, the cue was associated with fixed ratio responding for intravenous cocaine or food pellets in one context (Context A), followed by extinction in another context (Context B), where responding produced the cue in one group but did not produce the cue in the other group. Afterward, contextual renewal was assessed with and without the cue in Context A. During extinction, a cue previously associated with cocaine reinforcement caused an increase in responding initially (an extinction burst) and throughout 16 2-hr extinction sessions, as well as weakened contextual renewal when animals were tested with the cue in Context A. In contrast, there were few detectable effects of the cue on extinction and contextual renewal when food pellets were the reinforcer. In Experiment 2, effects of a cue during extinction of progressive ratio responding were revealed with food pellets when animals showed weakened responding on the initial trials of postextinction reacquisition sessions. These experiments demonstrate that the presence of a cue associated with reinforcement during extinction may prolong responding in the short term while creating a more persistent form of extinction that resists relapse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Presentation of unpaired unconditional stimuli during extinction reduces renewal of conditional fear and slows re-acquisition.

Past research has shown that presenting unconditional stimuli (US) during extinction training, either paired with the conditional stimulus (CS) or explicitly unpaired, can reduce spontaneous recovery and slow the re-acquisition of conditional fear. Whether contextual renewal of conditioned fear as indexed by electrodermal responses and self-report measures of anxiety and CS evaluations is also reduced after presentation of paired or unpaired USs during extinction training is currently unclear. Three groups of participants (Paired, Unpaired, Standard Extinction) completed a sequence of habituation, acquisition, extinction, renewal, and re-acquisition phases. During extinction, five CS-US pairings were presented in group Paired, whereas five US were presented alone in group Unpaired. No US were presented during standard extinction. For all groups, extinction was conducted in a context that was different from that of the other phases. Extinction of differential electrodermal responding was evident in groups Unpaired and Standard, but not in group Paired. Contextual renewal and fast re-acquisition, as indexed by differential electrodermal responding, were evident in group Standard, but not in group Unpaired and differential electrodermal responding persisted in group Paired. After extinction, self-reported anxiety was higher in groups Paired and Unpaired, but differential CS evaluations were evident in group Paired only. The current results suggest that presenting additional unpaired USs during extinction training strengthens extinction and protects against the renewal of differential electrodermal responding.

L-DOPA and consolidation of fear extinction learning among women with posttraumatic stress disorder

This study tested whether l-DOPA delivered during the consolidation window following fear extinction learning reduces subsequent fear responding among women with PTSD. Adult women diagnosed with PTSD completed a contextual fear acquisition and extinction task during fMRI and then immediately received either placebo (n = 34), 100/25 mg l-DOPA/carbidopa (n = 28), or 200/50 mg l-DOPA/carbidopa (n = 29). Participants completed a resting-state scan before the task and again 45 min following drug ingestion to characterize effects of l-DOPA on extinction memory neural reactivation patterns during consolidation. Twenty-four hours later, participants returned for tests of context renewal, extinction recall, and reinstatement during fMRI with concurrent skin conductance responding (SCR) assessment. Both active drug groups demonstrated increased reactivation of extinction encoding in the amygdala during the post-task resting-state scan. For SCR data, both drug groups exhibited decreased Day 2 reinstatement across all stimuli compared to placebo, and there was some evidence for decreased context renewal to the fear stimulus in the 100 mg group compared to placebo. For imaging data, both drug groups demonstrated decreased Day 2 reinstatement across stimuli in a bilateral insula network compared to placebo. There was no evidence in SCR or neural activity that l-DOPA improved extinction recall. Reactivation of extinction encodings in the amygdala during consolidation on Day 1 predicted Day 2 activation of the insula network. These results support a role for dopamine during the consolidation window in boosting reactivation of amygdala extinction encodings and reducing reinstatement, but not improving extinction recall, in women with PTSD.

Exploring the Contextual Renewal of Conditioned Attitudes After Counterconditioning

Research on contextualized attitude change suggests that, even when coun-terattitudinal information effectively influences evaluations in the context in which this information was learned, previously formed attitudes sometimes continue to determine evaluations in any other context (contextual renewal). Expanding on evidence for contextual renewal in attitude change based on verbal information, five experiments tested the emergence of contextual renewal in evaluative conditioning, involving pairings of a conditioned stimulus with a valenced unconditioned stimulus. Counter to the notion of contextual renewal, counterconditioning changed initially conditioned attitudes to the same extent irrespective of the context. Verbal information presented with the same procedural parameters produced contextual renewal effects only when evaluations were not measured between the formation of initial attitudes and the learning of counterattitudinal information. The results suggest two previously unidentified boundary conditions of contextualized attitude change that need to be reconciled with extant theories of evaluative learning.

Natural Regeneration Following Partial and Clear-Cut Harvesting in Mature Aspen-Jack Pine Stands in Eastern Canada

Over the last three decades, the ecological basis for the generalized use of even-aged silviculture in boreal forests has been increasingly challenged. In boreal mixed-wood landscapes, the diminishing proportion of conifers, to the benefit of intolerant hardwoods, has been a primary concern, coupled with the general rarefication of old-growth conifer-dominated stands. In this context, partial cutting, extended rotations and forest renewal techniques that eliminate or reduce regenerating hardwoods have been proposed as means of regaining greater conifer cover. As a result, experimentation and industrial application of various forms of both variable retention and partial harvesting are occurring across the commercial Canadian boreal forest. In this study, we compared the effects of two harvesting intensities, clearcutting and low-intensity partial cutting (removal of 25–31% of tree basal area), on hardwood and conifer regeneration levels 7–19 years following treatments in aspen (Populus tremuloides)-dominated stands and verified whether regeneration differences existed between micro-sites on and off machinery trails. The abundance of aspen regeneration increased with percent basal area removal and was positively correlated to the abundance of mature aspen prior to harvesting. The abundance of fir (Abies balsamea) regeneration after partial cutting was similar to controls and higher than after clear-cutting and was positively correlated with ground cover of mixed litter (i.e., mixture of needles and leaves) and negatively correlated with ground cover of broadleaf litter. These results suggest that it is possible in boreal mixed-woods to control aspen abundance and promote or maintain conifer regeneration through silvicultural treatments that limit canopy opening and promote mixed forest floor litter.

Exploring the Contextual Renewal of Conditioned Attitudes After Counterconditioning

Exploring the Contextual Renewal of Conditioned Attitudes After Counterconditioning

Behavioral and immunohistochemical characterization of rapid reconditioning following extinction of contextual fear.

A fundamental property of extinction is that the behavior that is suppressed during extinction can be unmasked through a number of postextinction procedures. Of the commonly studied unmasking procedures (spontaneous recovery, reinstatement, contextual renewal, and rapid reacquisition), rapid reacquisition is the only approach that allows a direct comparison between the impact of a conditioning trial before or after extinction. Thus, it provides an opportunity to evaluate the ways in which extinction changes a subsequent learning experience. In five experiments, we investigate the behavioral and neurobiological mechanisms of postextinction reconditioning. We show that rapid reconditioning of unsignaled contextual fear after extinction in male Long–Evans rats is associative and not affected by the number or duration of extinction sessions that we examined. We then evaluate c-Fos expression and histone acetylation (H4K8) in the hippocampus, amygdala, prefrontal cortex, and bed nucleus of the stria terminalis. We find that in general, initial conditioning has a stronger impact on c-Fos expression and acetylation than does reconditioning after extinction. We discuss implications of these results for theories of extinction and the neurobiology of conditioning and extinction.

Devaluation of threat memory using a dual-task intervention does not reduce context renewal of fear

Many patients who benefit from exposure-based therapy for anxiety disorders fail to maintain their gains. Learned fear may return when they encounter phobic stimuli in a different context than the one in which extinction occurred. In the current pre-registered experiment, we tested whether threat memory devaluation reduces context renewal of fear. A dual-task intervention was used to devalue threat memory. During this intervention, individuals recall the threat memory while simultaneously performing a demanding secondary task (e.g., making eye movements). On day 1, participants (N = 75) underwent fear acquisition with an aversive film clip in context A. On day 2, 25 participants were assigned to each group, namely a dual-task group, or one of two control groups: recall only task (without the dual-task) or no intervention. Afterwards, all participants underwent extinction training in context B and were then exposed to context A again in a test phase. The dual-task intervention effectively degraded threat memory compared to no intervention, but the recall only intervention was also partly effective. However, all three groups showed comparable fear renewal on subjective and physiological measures. This indicates that threat memory devaluation was not effective to prevent context renewal.

Context-Dependent and Context-Independent Effects of D1 Receptor Antagonism in the Basolateral and Central Amygdala during Cocaine Self-Administration.

One way that drugs of abuse perturb the dopamine system is by triggering large amounts of extracellular dopamine to efflux into limbic regions. The basolateral (BLA) and central (CeA) nuclei of the amygdala have been shown to play distinct roles in value representation of primary and conditioned reward. However, the precise role of dopaminergic receptors in the BLA and the CeA during reward-related behaviors remains to be determined. Here we investigate the effects of dopamine D1 receptor blockade in the BLA and the CeA during asymptotic performance of cocaine self-administration and in a novel application of contextual renewal under continued access conditions. After more than three weeks of chained seek-take self-administration of cocaine, male Long Evans rats were given a bilateral intra-BLA or intra-CeA infusion of the D1 antagonist SCH-23390 (2 µg/0.3 µl) for multiple days. Intra-BLA D1 receptor blockade before, but not after the self-administration session, gradually suppressed drug seeking and taking responses and persisted with a change in context with continued D1 blockade. In contrast, intra-CeA D1 receptor blockade caused a rapid reduction in self-administration that showed renewal with a change in context with continued D1 blockade. Further, conditioned place aversion developed with intra-BLA but not intra-CeA infusions. Collectively, these results demonstrate that dopamine D1 receptors in the BLA and CeA both contribute to drug seeking and taking, but may do so through distinct mechanisms.

Renewal of conditioned fear responses using a film clip as the aversive unconditioned stimulus

Background and objectivesPavlovian fear conditioning paradigms are valuable to investigate fear learning and the return of extinguished fear in the lab. However, their validity is limited, because the aversive stimuli (e.g., electric shocks) typically lack the modalities and complexity of real-world aversive experiences. To overcome this limitation, we examined fear acquisition, extinction and contextual renewal using an audiovisual unconditioned stimulus (US). MethodOn day 1, 50 healthy participants completed an acquisition phase in a specific context (i.e., desk or bookcase, ‘context A’). Pictures of colored lamps served as conditioned stimuli and an aversive film clip was used as US. On day 2, extinction took place in the same context (‘context A’) or in a different context (‘context B’). Afterwards, renewal was tested in the acquisition context (AAA vs. ABA design). ResultsAs hypothesized, fear acquisition and extinction, as measured by US expectancy ratings, fear potentiated startle (FPS), and skin conductance responses (SCRs), were successful. Most importantly, conditioned responding was renewed on all measures in the ABA condition, but not in the AAA condition. Differential renewal (i.e., larger renewal for CS + than for CS-) was only observed for US expectancy ratings. LimitationsThe return of conditioned responses was non-differential for FPS and SCR. ConclusionsThe current set-up enables investigation of fear renewal using an audiovisual US. Future studies can utilize this paradigm to investigate interventions that aim to reduce fear renewal by modifying the US memory, such as Eye Movement Desensitization and Reprocessing and imagery rescripting.

Effects of Noradrenergic Stimulation Upon Context-Related Extinction Learning Performance and BOLD Activation in Hippocampus and Prefrontal Cortex Differ Between Participants Showing and Not Showing Renewal.

While the neural structures mediating context-related renewal of extinction are well established, the neurotransmitter systems processing renewal remain elusive. Noradrenergic stimulation before extinction improved learning, but did not alter renewal. Since context processing already during initial conditioning can influence renewal, in this fMRI study we investigated how noradrenergic stimulation by a single dose of atomoxetine (ATO) before initial acquisition of a context-related predictive-learning task affects subsequent learning and renewal in humans. ATO participants showing contextual renewal (REN) exhibited a selective extinction learning deficit compared to placebo (PLAC) and ATO participants lacking renewal (ATO NoREN), probably owing to formation of more stable associations during acquisition. New learning and retrieval during the extinction phase as well as initial acquisition were unimpaired. In ATO REN, higher activation in right inferior frontal gyrus (iFG) during acquisition may have supported the formation of more stable associations, while reduced activation in hippocampus and left iFG during extinction was associated with impaired context encoding and response inhibition. During recall, ATO REN showed reduced overall context-dependent renewal associated with higher activation in medial PFC and right hippocampus. The results demonstrate the importance of noradrenergic processing in inferior frontal cortex and hippocampus for human extinction learning, but not necessarily initial conditioning. Since an identical atomoxetine treatment evoked diverging blood-oxygen level dependent (BOLD) activation patterns in REN and NoREN participants, the effect is presumably related to the participants’ preferred processing strategies that may have recruited differentially interconnected networks in which noradrenergic stimulation produced diverging consequences. In the ATO REN group, probably an additive effect of their preferred processing strategy, which pre-activated the noradrenergic system, and the experimental treatment caused a shift beyond the optimal working range of the noradrenergic system, thus modulating BOLD activation in a way that impaired extinction learning and recall.

Cholinergic Modulation of Exposure Disrupts Hippocampal Processes and Augments Extinction: Proof-of-Concept Study With Social Anxiety Disorder

BackgroundIn rodents, context specificity of Pavlovian extinction is attenuated by manipulations that impair hippocampal function, including systemic administration of scopolamine, a muscarinic-cholinergic receptor antagonist. Context renewal translates into return of fear following exposure therapy to feared situations. We evaluated the effectiveness of scopolamine for attenuating context renewal of phobic fear in humans. MethodsA total of 60 participants (35 female, 22 male, 1 transgender, 2 undeclared) with social anxiety disorder and fear of public speaking were randomized to placebo, 0.5 mg scopolamine, or 0.6 mg scopolamine. They completed seven exposure sessions in an exposure context and subsequently tested in the exposure context (extinction retest) versus a different context (context renewal test), which were counterbalanced. Testing 1 month later occurred in the exposure context (long-term extinction retest). Fear measures included skin conductance and self-reported distress during speeches. Hippocampus-dependent cognitive tasks were completed as well. ResultsScopolamine augmented extinction across exposure sessions on skin conductance response and skin conductance level. Lower skin conductance response at context renewal in scopolamine groups relative to the placebo group was constrained to simple effects and complicated by unexpected outcomes within placebo and on self-reported fear. Scopolamine led to lower skin conductance response at long-term extinction retest. Scopolamine impaired performance on a cognitive task of hippocampal function. ConclusionsNoninvasive and well-tolerated scopolamine impaired hippocampal processes and augmented extinction during exposure. Drug-free effects persisted 1 month later. Findings at context renewal were limited and suggestive only. Further investigation is warranted with varying scopolamine dosages.

Pathway specific activation of ventral hippocampal cells projecting to the prelimbic cortex diminishes fear renewal.

The ability to learn that a stimulus no longer signals danger is known as extinction. A major characteristic of extinction is that it is context-dependent, which means that fear reduction only occurs in the same context as extinction training. In other contexts, there is re-emergence of fear, known as contextual renewal. The ability to properly extinguish fear memories and generalize safety associations to multiple contexts provides therapeutic potential, but little is known about the specific neural pathways that mediate fear renewal and extinction generalization. The ventral hippocampus (VH) is thought to provide a contextual gating mechanism that determines whether fear or safety is expressed in particular contexts through its projections to areas of the fear circuit, including the infralimbic (IL) and prelimbic (PL) cortices. Moreover, VH principal cells fire in large, overlapping regions of the environment, a characteristic that is ideal to support generalization; yet it is unclear how different projection cells mediate this process. Using a pathway-specific (intersectional) chemogenetic approach, we demonstrate that selective activation of VH cells projecting to PL attenuates fear renewal without affecting fear expression. These results have implications for anxiety disorders since they uncover a neural pathway associated with extinction generalization.

Effects of a histone deacetylase 3 inhibitor on extinction and reinstatement of cocaine self-administration in rats

A challenge in treating substance use disorder is that successful treatment often does not persist, resulting in relapse and continued drug seeking. One approach to persistently weaken drug-seeking behaviors is to pair exposure to drug-associated cues or behaviors with delivery of a compound that may strengthen the inhibition of the association between drug cues and behavior. We evaluated whether a selective histone deacetylase 3 (HDAC3) inhibitor could promote extinction and weaken contextual control of operant drug seeking after intravenous cocaine self-administration. Male Long-Evans rats received a systemic injection of the HDAC3 inhibitor RGFP966 either before or immediately after the first extinction session. Persistence of extinction was tested over subsequent extinction sessions, as well as tests of reinstatement that included cue-induced reinstatement, contextual renewal, and cocaine-primed reinstatement. Additional extinction sessions occurred between each reinstatement test. We also evaluated effects of RGFP966 on performance and motivation during stable fixed ratio operant responding for cocaine and during a progressive ratio of reinforcement. RGFP966 administered before the first extinction session led to significantly less responding during subsequent extinction and reinstatement tests compared to vehicle-injected rats. Follow-up studies found that these effects were not likely due to a performance deficit or a change in motivation to self-administer cocaine, as injections of RGFP966 had no effect on stable responding during a fixed or progressive ratio schedule. In addition, RGFP966 administered just after the first extinction session had no effect during early extinction and reinstatement tests, but weakened long-term responding during later extinction sessions. These results suggest that a systemic injection of a selective HDAC3 inhibitor can enhance extinction and suppress reinstatement after cocaine self-administration. The finding that behavioral and pharmacological manipulations can be combined to decrease drug seeking provides further potential for treatment by epigenetic modulation.

Post-exposure cortisol administration does not augment the success of exposure therapy: A randomized placebo-controlled study

Cortisol administration prior to treatment can promote the efficacy of exposure-based treatments in specific phobia: cortisol has been proposed to reduce fear retrieval at the beginning of exposure and to enhance the acquisition and consolidation of corrective information learned during exposure. Whether cortisol exerts a beneficial therapeutic effect when given after exposure, e.g., by targeting the consolidation of new corrective information, has not been addressed so far to date. Here, we examined whether post-exposure cortisol administration promotes fear reduction and reduces return of fear following contextual change in specific phobia. Furthermore, the effect of cortisol on return of fear following contextual change (i.e., contextual renewal) was assessed. Patients with spider phobia (N = 43) were treated with a single session of in-vivo exposure, followed by cortisol administration (20 mg hydrocortisone) in a double-blind, placebo-controlled study design. Return of fear was assessed with behavioral approach tests (BATs) in the familiar therapy context (versus a novel unfamiliar context) at one-month and seven-month follow-up assessment. Exposure was effective in reducing fear from pre-treatment to post-treatment (i.e., 24 h after exposure) on fear-related behavioral (approach behavior during the BAT), psychophysiological (heart rate during the BAT) and subjective (fear during the BAT, spider-fear related questionnaires) measures of therapeutic outcome, with no add-on benefit of cortisol administration. Cortisol had no effect on contextual renewal at one-month follow-up. However, in a subsample (N = 21) that returned to the seven-month follow-up, an adverse effect of cortisol on fear renewal was found, with cortisol-treated patients showing an increase in subjective fear at the final approach distance of the BAT from post-treatment to seven-month follow-up. These and previous findings underline the importance of considering the exact timing of cortisol application when used as an add-on treatment for extinction-based psychotherapy: post-exposure cortisol administration does not seem to be effective, but might promote fear renewal at the subjective level.

Inhibitory Learning for Anxiety-Related Disorders

This article reviews the articles in this issue that describe the strategies derived from the inhibitory learning model as applied to exposure therapy for anxiety disorders. The major principles of inhibitory learning are to create and strengthen nonthreat associations in memory (largely by engaging prefrontal cortical regions), and to effectively retrieve those nonthreat associations in the long term. Several case vignettes are provided that demonstrate how the principles of inhibitory learning (which include maximizing expectancy violations, limiting distraction, fear antagonistic actions, deepened extinction, elimination of safety behaviors, occasional reinforced extinction, increasing variability of exposures and offsetting reinstatement and context renewal effects) can be applied in clinical practice.