Effects of cortisol on retrieval of extinction memory in individuals with social anxiety.
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ABSTRACT:
SUBMITTER: Moriishi C
PROVIDER: S-EPMC9216654 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RATIONALE:A promising strategy to prevent a return of fear after exposure-based therapy in anxiety disorders is to pharmacologically enhance the extinction memory consolidation presumed to occur after exposure. Accumulating evidence suggests that the effect of a number of pharmacological consolidation enhancers depends on a successful fear reduction during exposure. Here, we employed the dopamine precursor L-DOPA to clarify whether its documented potential to enhance extinction memory consolidation is dependent on successful fear extinction. METHODS:In two double-blind, randomized and placebo-controlled experiments (experiment 1: N = 79, experiment 2: N = 32) comprising fear conditioning (day 1), extinction followed by administration of 150 mg L-DOPA or placebo (day 2) and a memory test (day 3) in healthy male adults, conditioned responses were assessed as differential skin conductance responses. We tested whether the effect of L-DOPA on conditioned responses at test depended on conditioned responses at the end of extinction in an experiment with a short (10 trials, experiment 1) and long (25 trials, experiment 2) extinction session. RESULTS:In both experiments, the effect of L-DOPA was dependent on conditioned responses at the end of extinction. That is, post-extinction L-DOPA compared to placebo administration reduced conditioned responses at test only in participants showing a complete reduction of conditioned fear at the end of extinction. CONCLUSION:The results support the potential use of L-DOPA as a pharmacological adjunct to exposure treatment, but point towards a common boundary condition for pharmacological consolidation enhancers: a successful reduction of fear in the exposure session.
| S-EPMC6892771 | biostudies-literature
Project description: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.
| S-EPMC5766663 | biostudies-literature
Project description:Disruption of drug-associated memory reduces relapse. Transient memory retrieval facilitates the upcoming extinction of addiction memory, while the neural basis for this beneficial outcome remains unelucidated. Here, we report that AMPA receptor trafficking acts as the central component for retrieval-extinction-based drug memory intervention. Drug memory retrieval transiently reduces AMPA receptor-mediated synaptic transmission in prefrontal cortical neurons (lasting for 2 to 4 hours) through rapid removal of calcium-permeable AMPA receptors from the synapse, which returned to basal state level after 6 hours. The receptor trafficking is orchestrated by dopamine D1 but not D2 receptor signaling. Blocking AMPA receptor trafficking abolishes retrieval-extinction-mediated addiction memory degradation. These results reveal the molecular mechanism underlying the efficacy of transient memory retrieval on helping to erase addiction memory and support targeting the prefrontal cortex to reduce relapse (e.g., with noninvasive brain stimulation).
| S-EPMC9788760 | biostudies-literature
Project description:Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts. In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking. In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence.
| S-EPMC3695463 | biostudies-literature
Project description:Extinction of conditioned fear embodies a crucial mechanism incorporated in exposure therapy. Clinical studies demonstrated that application of the stress hormone cortisol before exposure sessions facilitates exposure success, but the underlying neural correlates remain unknown. Context- and stimulus-dependent cortisol effects on extinction learning will be characterized in this study and tested in the extinction and in a new context. Forty healthy men participated in a 3-day fear conditioning experiment with fear acquisition in context A (day 1), extinction training in context B (day 2), and recall in context B and a new context C one week later (day 3). Hydrocortisone (30 mg) or placebo was given before extinction training. Blood-oxygen-level-dependent responses and skin conductance responses (SCRs) served as dependent measures. At the beginning of extinction training, cortisol reduced conditioned SCRs, diminished activation of the amygdala-hippocampal complex, and enhanced functional connectivity of the anterior parahippocampal gyrus with the ventromedial prefrontal cortex (vmPFC). After one week, the cortisol group showed increased hippocampal activation and connectivity to the vmPFC toward an extinguished stimulus and reduced insula activation toward a nonextinguished stimulus in the extinction context. However, this inhibitory cortisol effect did not extend to the new context. Taken together, cortisol reduced fear recall at the beginning of extinction and facilitated the consolidation of the extinction memory as evidenced by an inhibitory activation pattern one week later. The stress hormone exerted a critical impact on the amygdala-hippocampus-vmPFC network underlying fear and extinction memories. However, cortisol did not attenuate the context dependency of extinction.
| S-EPMC5729571 | biostudies-literature
Project description:Over a dozen studies have examined the efficacy of post-retrieval extinction (PRE) in healthy adults in the fear conditioning laboratory, with a recent meta-analysis reporting an overall small-moderate effect on attenuating the return of fear compared to standard extinction. The current study was designed to extend PRE effects to a mixed sample of healthy and anxious individuals, explore potential moderators, and examine the benefit of PRE for a memory conditioned over multiple days. Healthy (n = 49) and anxious (n = 43) adults received either one day of acquisition followed by PRE, one day of acquisition followed by extinction, or three days of acquisition followed by PRE. Comparing participants who received one day of acquisition followed by PRE or extinction, no significant effect of PRE was observed on differential skin conductance response reinstatement or reactivity to the conditioned stimulus alone. Anxiety symptoms did not moderate outcomes. There was no difference in return of fear for anxious participants who received three days of acquisition followed by PRE versus one day of acquisition followed by PRE. These results further highlight the variability of findings in the PRE literature and need for further examination of individual difference factors that may moderate PRE effects.
| S-EPMC7437718 | biostudies-literature
Project description:RationaleMemories can return to a labile state and become amenable to modification by pharmacological and behavioral manipulations after retrieval. This process may reduce the impact of aversive memories and provide a promising therapeutic technique for the treatment of anxiety disorders. A growing body of evidence suggests that the mammalian neuropeptide oxytocin (OT) plays a role in the regulation of emotional memories in animals. However, the effects of OT on threat memory in humans remain largely unknown.ObjectivesThis study aimed to investigate the effects of OT administration following threat memory retrieval on subsequent memory expression in human participants.MethodsIn a double-blind, randomized, placebo-controlled, between-subject design, 61 healthy human individuals completed a 3-day experiment. All the participants underwent threat conditioning on day 1. On day 2, the participants were randomized to receive an intranasal dose of OT (40 IU) or placebo after memory retrieval, or an intranasal dose of OT (40 IU) without retrieval. On day 3, the participants were tested for extinction and reinstatement.ResultsOn day 3, all groups showed equivalent stimulus discrimination during the early phase of extinction. However, the group that received OT following a memory reminder showed a greater decline in stimulus discrimination by the late phase of extinction relative to the two other groups.ConclusionsThe results indicate that OT did not block reconsolidation to prevent the return of threat memory but rather interacted with post-retrieval processes to facilitate next day extinction. The study provides novel preliminary evidence for the role of OT in human threat memory.
| S-EPMC6374199 | biostudies-literature
Project description:Current learning theories are based on the idea that learning is driven by the difference between expectations and experience (the delta rule). In extinction, one learns that certain expectations no longer apply. Here, we test the potential validity of the delta rule by manipulating memory retrieval (and thus expectations) during extinction learning. Adrenergic signaling is critical for the time-limited retrieval (but not acquisition or consolidation) of contextual fear. Using genetic and pharmacologic approaches to manipulate adrenergic signaling, we find that long-term extinction requires memory retrieval but not conditioned responding. Identical manipulations of the adrenergic system that do not affect memory retrieval do not alter extinction. The results provide substantial support for the delta rule of learning theory. In addition, the timing over which extinction is sensitive to adrenergic manipulation suggests a model whereby memory retrieval occurs during, and several hours after, extinction learning to consolidate long-term extinction memory.
| S-EPMC1166608 | biostudies-literature
Project description:Positive memory retrieval generates pleasant feelings that can counteract negative affective states and improve mood. However, not all positive memories are created equal. Our most treasured memories are likely experiences we shared with other people (e.g., birthday party) rather than something we did alone (e.g., receiving good grades). Here, we explored whether the social context within a positive memory enhanced its subjective value and contributed to an individual's well-being. In Study 1, participants were asked how much they would be willing to pay to reexperience positive memories that occurred with socially close others (high-social), with acquaintances (low-social) or alone (nonsocial). When controlling for the memory's positivity, participants were still willing to pay 1.5 times as much for high-social than for low-social or nonsocial memories. Likewise, participants chose to reminisce about high-social memories more frequently than less social ones of equal positive feeling. In Study 2, recalling memories rich in social context recruited regions previously implicated in mentalizing and reward (e.g., caudate), which further correlated with greater ability to savor positive emotions in daily life. Finally, we examined the benefit of social context by asking participants to recall positive memories that varied in social context after acute stress exposure. In Study 3, recalling memories that included higher social context led to a greater dampening of the physiological stress response (i.e., cortisol). Taken together, these findings suggest that social context inherent in a positive memory enhances its value, providing a possible mechanism by which positive reminiscence aids stress coping and enhances well-being. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
| S-EPMC7048660 | biostudies-literature
Project description:BACKGROUND:Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. METHODS:In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. RESULTS:Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. CONCLUSIONS:These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear.
| S-EPMC4480632 | biostudies-literature