Extinction Group Research Articles

Investigating the role of dopamine receptor- and parvalbumin-expressing cells in extinction of conditioned fear

The present study examined the pattern of activation of neurons that express dopamine receptors 1 and 2 (D1R and D2R), and parvalbumin (PV) in mice that underwent extinction of a fear memory. Adult male transgenic mice expressing D1R or D2R tagged with green fluorescent protein (GFP) were conditioned with 6 tone-shock pairings. The following day they were randomly divided into one of four experimental groups: extinction, retrieval, context or handled. Extinction groups were exposed to 45 tone presentations, retrieval groups were exposed to 5 tone presentations and the context groups were exposed to the chamber without any tones. Ninety minutes following their assigned treatment, mice were perfused and brain tissue processed for Fos/GFP/PV immunohistochemistry. Quantification of immunoreactivity revealed that extinction resulted in changes in the infralimbic cortex including increased Fos expression and a decrease in the number of D2R+ cells compared to all other groups. Conversely, fear memory retrieval resulted in increased activation of D2R+ cells in the prelimbic cortex compared to all other groups. Additional changes were observed in the extinction and retrieval groups that were different to the handled group, but not to the context group, which highlights that there is overlapping neurocircuitry between extinction and retrieval of fear memory, as well as with context exposure. These results provide novel insights into the roles of specific dopamine receptor subtypes, which will be valuable for informing future research that aims to strengthen extinction learning via dopaminergic mechanisms.

Building physiological toughness: Some aversive events during extinction may attenuate return of fear

Background and objectivesAlthough exposure therapy is an effective treatment for anxiety disorders, fear sometimes returns following successful therapy. Recent literature in animal models indicates that incorporating some aversive events into extinction training may offset these return of fear effects. MethodsThe effect of occasional reinforced extinction trials was investigated in a sample of thirty-nine participants using a fear conditioning and extinction paradigm. Participants either underwent traditional extinction procedures during which the conditional stimulus which had been paired with the unconditional stimulus (US) during acquisition training (CS+) was presented alone with no presentations of the US or partially reinforced extinction during which there were several unpredicted CS+/US pairings. ResultsAs measured by skin conductance responses, physiological fear responding remained elevated during extinction for participants who experienced partially reinforced extinction; however, these participants demonstrated protection from rapid reacquisition effects. Results from the subjective US-expectancy ratings did not provide evidence of protection against rapid reacquisition in the partially reinforced extinction group; however, there was evidence of protection from spontaneous recovery effects. Lastly, as measured by valence ratings, it was unclear whether partially reinforced extinction provided protection from fear recovery effects. LimitationsAlthough participants who experienced partially reinforced extinction demonstrated protection from rapid reacquisition as measured by skin conductance responses, they also demonstrated significantly higher levels of physiological fear responding during extinction which made the results of the spontaneous recovery test more difficult to interpret. ConclusionsOccasional CS-US pairings during extinction may protect against return of fear effects. Clinical implications are discussed.

Classification of crystal structure using a convolutional neural network.

A deep machine-learning technique based on a convolutional neural network (CNN) is introduced. It has been used for the classification of powder X-ray diffraction (XRD) patterns in terms of crystal system, extinction group and space group. About 150 000 powder XRD patterns were collected and used as input for the CNN with no handcrafted engineering involved, and thereby an appropriate CNN architecture was obtained that allowed determination of the crystal system, extinction group and space group. In sharp contrast with the traditional use of powder XRD pattern analysis, the CNN never treats powder XRD patterns as a deconvoluted and discrete peak position or as intensity data, but instead the XRD patterns are regarded as nothing but a pattern similar to a picture. The CNN interprets features that humans cannot recognize in a powder XRD pattern. As a result, accuracy levels of 81.14, 83.83 and 94.99% were achieved for the space-group, extinction-group and crystal-system classifications, respectively. The well trained CNN was then used for symmetry identification of unknown novel inorganic compounds.

Active Avoidance: Neural Mechanisms and Attenuation of Pavlovian Conditioned Responding.

Patients with anxiety disorders often experience a relapse in symptoms after exposure therapy. Similarly, threat responses acquired during Pavlovian threat conditioning often return after extinction learning. Accordingly, there is a need for alternative methods to persistently reduce threat responding. Studies in rodents have suggested that exercising behavioral control over an aversive stimulus can persistently diminish threat responses, and that these effects are mediated by the amygdala, ventromedial prefrontal cortex, and striatum. In this fMRI study, we attempted to translate these findings to humans. Subjects first underwent threat conditioning. We then contrasted two forms of safety learning: active avoidance, in which participants could prevent the shock through an action, and yoked extinction, with shock presentation matched to the active condition, but without instrumental control. The following day, we assessed subjects' threat responses (measured by skin conductance) to the conditioned stimuli without shock. Subjects next underwent threat conditioning with novel stimuli. Yoked extinction subjects showed an increase in conditioned response to stimuli from the previous day, but the active avoidance group did not. Additionally, active avoidance subjects showed reduced conditioned responding during novel threat conditioning, but the extinction group did not. We observed between-group differences in striatal BOLD responses to shock omission in Avoidance/Extinction. These findings suggest a differential role for the striatum in human active avoidance versus extinction learning, and indicate that active avoidance may be more effective than extinction in persistently diminishing threat responses.SIGNIFICANCE STATEMENT Extinguished threat responses often reemerge with time, highlighting the importance of identifying more enduring means of attenuation. We compared the effects of active avoidance learning and yoked extinction on threat responses in humans and contrasted the neural circuitry engaged by these two processes. Subjects who learned to prevent a shock through an action maintained low threat responses after safety learning and showed attenuated threat conditioning with novel stimuli, in contrast to those who underwent yoked extinction. The results suggest that experiences of active control over threat engage the striatum and promote a shift from expression of innate defensive responses toward more adaptive behavioral responses to threatening stimuli.

The effects of instructions on the sensitivity of negatively reinforced human behavior to extinction

The effects of instructions on the sensitivity of negatively reinforced (escape) behavior to extinction were studied. Initially, responding produced timeouts from pressing a force cell on a variable-ratio (VR) schedule, which was then discontinued (extinction). Based on extinction data, participants were distributed into two groups. Participants in the Extinction Group (for which response rates were low in extinction) were instructed that the experimenter expected them to continue responding in extinction after a second exposure to the VR schedule. Participants in the Persistence group (for which response rates were high in extinction) were instructed that the experimenter expected them to stop responding in extinction. Relative to the condition in which instructions were absent, extinction-response rates increased and decreased, respectively, for participants in the Persistence and Extinction groups. These results replicate and extend to negatively reinforced responding previous findings that showed behavioral control by instructions formulated as explicit experimenter demands or expectations.

Slower reacquisition after partial extinction in human contingency learning.

Extinction is a very relevant learning phenomenon from a theoretical and applied point of view. One of its most relevant features is that relapse phenomena often take place once the extinction training has been completed. Accordingly, as extinction-based therapies constitute the most widespread empirically validated treatment of anxiety disorders, one of their most important limitations is this potential relapse. We provide the first demonstration of relapse reduction in human contingency learning using mild aversive stimuli. This effect was found after partial extinction (i.e., reinforced trials were occasionally experienced during extinction, Experiment 1) and progressive extinction treatments (Experiment 3), and it was not only because of differences in uncertainty levels between the partial and a standard extinction group (Experiment 2). The theoretical explanation of these results, the potential uses of this strategy in applied situations, and its current limitations are discussed. (PsycINFO Database Record

Physical properties of CO-dark molecular gas traced by C+

Neither HI nor CO emission can reveal a significant quantity of so-called dark gas in the interstellar medium (ISM). It is considered that CO-dark molecular gas (DMG), the molecular gas with no or weak CO emission, dominates dark gas. We identified 36 DMG clouds with C$^+$ emission (data from Galactic Observations of Terahertz C+ (GOT C+) project) and HINSA features. Based on uncertainty analysis, optical depth of HI $\tau\rm_{HI}$ of 1 is a reasonable value for most clouds. With the assumption of $\tau\rm_{HI}=1$, these clouds were characterized by excitation temperatures in a range of 20 K to 92 K with a median value of 55 K and volume densities in the range of $6.2\times10^1$ cm$^{-3}$ to $1.2\times 10^3$ cm$^{-3}$ with a median value of $2.3\times 10^2$ cm$^{-3}$. The fraction of DMG column density in the cloud ($f\rm_{DMG}$) decreases with increasing excitation temperature following an empirical relation $f\rm_{DMG}=-2.1\times 10^{-3}T_(ex,\tau_{HI}=1)$+1.0. The relation between $f\rm_{DMG}$ and total hydrogen column density $N_H$ is given by $f\rm_{DMG}$=$1.0-3.7\times 10^{20}/N_H$. The values of $f\rm_{DMG}$ in the clouds of low extinction group ($A\rm_V \le 2.7$ mag) are consistent with the results of the time-dependent, chemical evolutionary model at the age of ~ 10 Myr. Our empirical relation cannot be explained by the chemical evolutionary model for clouds in the high extinction group ($A\rm_V > 2.7$ mag). Compared to clouds in the low extinction group ($A\rm_V \le 2.7$ mag), clouds in the high extinction group ($A\rm_V > 2.7$ mag) have comparable volume densities but excitation temperatures that are 1.5 times lower. Moreover, CO abundances in clouds of the high extinction group ($A\rm_V > 2.7$ mag) are $6.6\times 10^2$ times smaller than the canonical value in the Milky Way. #[Full version of abstract is shown in the text.]#

Immediate Extinction Attenuates Spontaneous Recovery and Reinstatement in a Passive Avoidance Paradigm.

Recent research suggests that extinction occurring shortly after fear conditioning attenuates spontaneous recovery and reinstatement of fear. Two experiments investigated whether immediate extinction would prevent spontaneous recovery and reinstatement of fear using a passive avoidance paradigm. In Experiment 1, naive female adult rats (N = 40) received extinction training either immediately or 24 hours (delayed) after fear conditioning. Both extinction groups showed a significant reduction in fear at a 1-day test. At a 15-day test, spontaneous recovery was observed in the delayed extinction group while the immediate extinction group continued to show significant extinction. In Experiment 2, using a naive group of adult female rats (N = 16), the extinction result was replicated in both the immediate and delayed extinction groups at the 1-day interval. Reinstatement of fear, elicited by foot-shock in a neutral environment, was observed for the delayed group but not for the immediate group. By utilizing the passive-avoidance paradigm, these experiments replicate and extend previous findings that immediate extinction attenuates spontaneous recovery and reinstatement of fear.

Behavioral Interventions for Infant Sleep Problems: A Randomized Controlled Trial.

To evaluate the effects of behavioral interventions on the sleep/wakefulness of infants, parent and infant stress, and later child emotional/behavioral problems, and parent-child attachment. A total of 43 infants (6-16 months, 63% girls) were randomized to receive either graduated extinction (n = 14), bedtime fading (n = 15), or sleep education control (n = 14). Sleep measures included parent-reported sleep diaries and infant actigraphy. Infant stress was measured via morning and afternoon salivary cortisol sampling, and mothers' self-reported mood and stress. Twelve months after intervention, mothers completed assessments of children's emotional and behavioral problems, and mother-child dyads underwent the strange situation procedure to evaluate parent-child attachment. Significant interactions were found for sleep latency (P < .05), number of awakenings (P < .0001), and wake after sleep onset (P = .01), with large decreases in sleep latency for graduated extinction and bedtime fading groups, and large decreases in number of awakenings and wake after sleep onset for the graduated extinction group. Salivary cortisol showed small-to-moderate declines in graduated extinction and bedtime fading groups compared with controls. Mothers' stress showed small-to-moderate decreases for the graduated extinction and bedtime fading conditions over the first month, yet no differences in mood were detected. At the 12-month follow-up, no significant differences were found in emotional and behavioral problems, and no significant differences in secure-insecure attachment styles between groups. Both graduated extinction and bedtime fading provide significant sleep benefits above control, yet convey no adverse stress responses or long-term effects on parent-child attachment or child emotions and behavior.

Reductions in Children’s Vicariously Learnt Avoidance and Heart Rate Responses Using Positive Modeling

Recent research has indicated that vicarious learning can lead to increases in children’s fear beliefs and avoidance preferences for stimuli and that these fear responses can subsequently be reversed using positive modeling (counterconditioning). The current study investigated children’s vicariously acquired avoidance behavior, physiological responses (heart rate), and attentional bias for stimuli and whether these could also be reduced via counterconditioning. Ninety-six (49 boys, 47 girls) 7- to 11-year-olds received vicarious fear learning for novel stimuli and were then randomly assigned to a counterconditioning, extinction, or control group. Fear beliefs and avoidance preferences were measured pre- and post-learning, whereas avoidance behavior, heart rate, and attentional bias were all measured post-learning. Control group children showed increases in fear beliefs and avoidance preferences for animals seen in vicarious fear learning trials. In addition, significantly greater avoidance behavior, heart rate responding, and attentional bias were observed for these animals compared to a control animal. In contrast, vicariously acquired avoidance preferences of children in the counterconditioning group were significantly reduced post-positive modeling, and these children also did not show the heightened heart rate responding to fear-paired animals. Children in the extinction group demonstrated comparable responses to the control group; thus the extinction procedure showed no effect on any fear measures. The findings suggest that counterconditioning with positive modelling can be used as an effective early intervention to reduce the behavioral and physiological effects of vicarious fear learning in childhood.

Comparing Counterconditioning and Extinction as Methods to Reduce Fear of Movement-Related Pain

Cognitive-behavioral treatments for chronic pain typically target pain-related fear; exposure in vivo is a common treatment focusing on disconfirming harm expectancy of feared movements. Exposure therapy is tailored on Pavlovian extinction; an alternative fear reduction technique that also alters stimulus valence is counterconditioning. We compared both procedures to reduce pain-related fear using a voluntary joystick movement paradigm. Participants were randomly allocated to the counterconditioning or extinction group. During fear acquisition, moving the joystick in 2 directions (conditioned stimulus [CS+]) was followed by a painful electrocutaneous stimulus (pain-unconditioned stimulus [US]), whereas moving the joystick in 2 other directions was not (CS−). During fear reduction, 1 CS+ was extinguished, but another CS+ was still followed by pain in the extinction group; in the counterconditioning group, 1 CS+ was extinguished and followed by a monetary reward-US, and another CS+ was followed by both USs (pain-US and reward-US). The results indicate that counterconditioning effectively reduces pain-related fear but that it does not produce deeper fear reduction than extinction. Adding a reward-US to a painful movement attenuated neither fear nor the intensity/unpleasantness of the pain. Both procedures changed stimulus valence. We contend that changing the affective valence of feared movements might improve fear reduction and may prevent relapse. PerspectiveThis article reports no immediate differences between counterconditioning and extinction in reducing pain-related fear in the laboratory. Unexpectedly, both methods also altered stimulus valence. However, we cautiously suggest that methods explicitly focusing on altering the affective valence of feared movements may improve the long-term effectiveness of fear reduction and prevent relapse.

Relapse of generalized bait shyness in rats after constant and graded extinction procedures

Oral ingestion of a toxic lithium chloride (LiCl) solution yields a conditioned aversion to a safe sodium chloride (NaCl) solution in rats, presumably because of the common quality of saltiness. By using this generalized bait-shyness paradigm, we examined the relapse of acquired and subsequently extinguished salty taste aversion. After conditioning by oral ingestion of a 0.15M LiCl solution, extinction was induced by two different experimental procedures. In the constant extinction group, rats were repeatedly exposed to 0.15M NaCl solution. For rats in the graded extinction group, the concentration of NaCl was gradually increased from a low level to 0.15M and an additional interfering sweet taste was gradually faded out. Rats in the graded extinction group were more prone to relapse than animals that underwent the constant extinction treatment. This difference was manifested in the following three response reoccurrence phenomena: renewal upon return to the acquisition context (Experiments 1A–C), spontaneous recovery after a 23-day interval (Experiment 2), and reacquisition caused by the second LiCl intake (Experiment 3). Theoretical and clinical implications of these results are discussed.

Compound Extinction

Although exposure therapy is an effective treatment for anxiety disorders, fear sometimes returns following successful therapy. The Rescorla–Wagner model predicts that presenting two fear-provoking stimuli simultaneously (compound extinction) will maximize learning during exposure and reduce the likelihood of relapse. Participants were presented with either single extinction trials only or single extinction trials followed by compound extinction trials. In addition, participants within each extinction group were randomized to caffeine or placebo ingestion prior to extinction to investigate the mechanism by which compound extinction may maximize learning (enhanced associative change or enhanced responding). Participants presented with compound trials demonstrated significantly less fear responding at spontaneous recovery compared with participants who received single extinction trials only. Ingestion of caffeine also provided some protection from spontaneous recovery (as measured by valence ratings). At the reinstatement test, only compound extinction trials predicted less fear responding; caffeine ingestion prior to extinction did not attenuate reinstatement effects.

Extinction in multiple virtual reality contexts diminishes fear reinstatement in humans

Although conditioned fear can be effectively extinguished by unreinforced exposure to a threat cue, fear responses tend to return when the cue is encountered some time after extinction (spontaneous recovery), in a novel environment (renewal), or following presentation of an aversive stimulus (reinstatement). As extinction represents a context-dependent form of new learning, one possible strategy to circumvent the return of fear is to conduct extinction across several environments. Here, we tested the effectiveness of multiple context extinction in a two-day fear conditioning experiment using 3-D virtual reality technology to create immersive, ecologically-valid context changes. Fear-potentiated startle served as the dependent measure. All three experimental groups initially acquired fear in a single context. A multiple extinction group then underwent extinction in three contexts, while a second group underwent extinction in the acquisition context and a third group underwent extinction in a single different context. All groups returned 24h later to test for return of fear in the extinction context (spontaneous recovery) and a novel context (renewal and reinstatement/test). Extinction in multiple contexts attenuated reinstatement of fear but did not reduce spontaneous recovery. Results from fear renewal were tendential. Our findings suggest that multi-context extinction can reduce fear relapse following an aversive event – an event that often induces return of fear in real-world settings – and provides empirical support for conducting exposure-based clinical treatments across a variety of environments.

Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core

Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10mg/kg) experimental mice acquired a morphine CPP dose response with 10mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction.

Can the morphology of deep-sea benthic foraminifera reveal what caused their extinction during the mid-Pleistocene Climate Transition?

Over 100 cosmopolitan species of deep-sea benthic foraminifera (Extinction Group, Ext. Gp) became extinct during the late Pliocene-middle Pleistocene (3.6–0.55 Ma). Most had elongate, cylindrical tests and terminal apertures with complex modifications. This study provides new hypotheses on the functions of the morphologies that characterised the Ext. Gp and how these features could have been associated with their demise. From our functional morphological analysis we infer that: i) their elongate cylindrical or flabelliform tests, combined with fine perforations and a complex terminal apertural face are indicative of infaunal k-strategists with a low rate of metabolism; and ii) their complex apertural faces may also have been an adaptation for gathering or processing their specific phytodetrital food. We propose three alternative hypotheses for the cause of these extinctions, and where possible test them using our high resolution micropaleontological and geochemical record through the last 1.07 Ma in lower bathyal site MD 97-2114 in the SW Pacific Ocean. Hypothesis 1 is that the Ext. Gp species were unable to adapt to increased variability in the overall quantity or pulsed seasonality of the food supply to the sea floor and were out-competed by opportunistic r-strategist benthic foraminifera. This is supported by the highly variable and increasing abundance of opportunistic foraminifera at our study site during the final phase of the extinction in the mid-Pleistocene Climate Transition, MPT. We doubt however, that there was increased variability in phytoplankton productivity throughout the world's oceans sufficient to bring about the global demise of the Ext. Gp. Hypothesis 2 is that lowered pCO 2 during increasingly severe MPT glacials, which coincided with the final phases of the extinction, may have caused the decline and possible loss of the Ext. Gp's phytoplankton food source. Declining pCO 2 during Neogene cooling was coeval with declining relative abundance of the Ext. Gp and reticulofenestrid nannofossils, but the final demise of this latter phytoplankton group occurred slightly later than the MPT in our study site and cannot be implicated with the extinction. If this hypothesis has any validity maybe the phytoplankton group left no fossil record. Our third alternative hypothesis is that maybe our Ext. Gp had much common DNA which made them the selective target of pathogens that caused their extinction. This does not easily explain their earlier disappearance at abyssal depths than at bathyal depths in our study region, which can be accommodated by hypotheses 1 and 2. • Functional morphology of Extinction group suggests they had low rates of metabolism. • Lowered pCO 2 during MPT glacials caused the decline of reticulofenestrid nannofossils. • Ext. Gp species may have been out-competed by opportunistic benthic foraminifera. • Ext. Gp demise was probably caused by the loss of a particular phytoplankton group particular phytoplankton.

Dendritic structural plasticity in the basolateral amygdala after fear conditioning and its extinction in mice

Previous research suggests that morphology and arborization of dendritic spines change as a result of fear conditioning in cortical and subcortical brain regions. This study uniquely aims to delineate these structural changes in the basolateral amygdala (BLA) after both fear conditioning and fear extinction. C57BL/6 mice acquired robust conditioned fear responses (70–80% cued freezing behavior) after six pairings with a tone cue associated with footshock in comparison to unshocked controls. During fear acquisition, freezing behavior was significantly affected by both shock exposure and trial number. For fear extinction, mice were exposed to the conditioned stimulus tone in the absence of shock administration and behavioral responses significantly varied by shock treatment. In the retention tests over 3 weeks, the percentage time spent freezing varied with the factor of extinction training. In all treatment groups, alterations in dendritic plasticity were analyzed using Golgi–Cox staining of dendrites in the BLA. Spine density differed between the fear conditioned group and both the fear extinction and control groups on third order dendrites. Spine density was significantly increased in the fear conditioned group compared to the fear extinction group and controls. Similarly in Sholl analyses, fear conditioning significantly increased BLA spine numbers and dendritic intersections while subsequent extinction training reversed these effects. In summary, fear extinction produced enduring behavioral plasticity that is associated with a reversal of alterations in BLA dendritic plasticity produced by fear conditioning. These neuroplasticity findings can inform our understanding of structural mechanisms underlying stress-related pathology can inform treatment research into these disorders.

Gating of Fear in Prelimbic Cortex by Hippocampal and Amygdala Inputs

The prefrontal cortex (PFC) regulates emotional responses, but it is unclear how PFC integrates diverse inputs to select the appropriate response. We therefore evaluated the contribution of basolateral amygdala (BLA) and ventral hippocampus (vHPC) inputs to fear signaling in the prelimbic (PL) cortex, a PFC region critical for the expression of conditioned fear. In conditioned rats trained to press for food, BLA inactivation decreased the activity of projection cells in PL, and reduced PL conditioned tone responses. In contrast, vHPC inactivation decreased activity of interneurons in PL and increased PL conditioned tone responses. Consistent with hippocampal gating of fear after extinction, vHPC inactivation increased fear and PL pyramidal activity in extinguished, but not in conditioned, rats. These results suggest a prefrontal circuit whereby hippocampus gates amygdala-based fear. Thus, deficient hippocampal inhibition of PFC may underlie emotional disorders, especially in light of reduced hippocampal volume observed in depression and PTSD.

Context-Induced Relapse to Alcohol Seeking After Punishment in a Rat Model

Rat studies have demonstrated that exposure to environments associated with alcohol intake reinstates alcohol seeking after extinction of alcohol-reinforced responding in a different context. However, extinction is limited as an abstinence model, because humans typically abstain because of negative consequences associated with excessive drinking. It is currently unknown whether alcohol-associated contexts can provoke relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences in a different context. Alcohol-preferring P rats were first given home-cage access to 20% ethanol. Next, they were trained to self-administer 20% ethanol in one context (context A). Subsequently, all rats continued to self-administer alcohol in a different context (context B). For one group, 50% of alcohol-reinforced responses were punished by mild footshock; two other groups either received noncontingent shocks or no shock. A fourth group was given extinction training in context B. All rats were then tested for relapse to alcohol seeking under extinction conditions in contexts A and B. In Context B, alcohol-taking behavior was suppressed by contingent shock (punishment) and extinction training but not by noncontingent shock. In Context A, relapse to alcohol seeking was reliably observed in the punished and extinction groups; a context switch had no effect on alcohol seeking in the no-shock or noncontingent shock groups. Our data indicate that punishment-induced suppression of alcohol-taking behavior is context-dependent. We propose that our procedure can be used to explore mechanisms of context-induced relapse to alcohol seeking after alcohol-taking behavior is suppressed by adverse consequences.

Reduction of fear of movement-related pain and pain-related anxiety: An associative learning approach using a voluntary movement paradigm

The fear-avoidance model advances fear of pain as a key factor in the origins of chronic pain disability. Initial evidence in those with chronic back pain reveals that exposure therapy reduces fear levels, disability, and pain. Despite the success of exposure in the clinic, fundamental research about its underlying mechanisms lags behind. Using a conditioning paradigm with movements as conditioned stimuli (CS) and a painful shock as unconditioned stimuli (US), we investigated the extinction of experimental fear of movement-related pain and pain-related anxiety (respectively induced by predictable and unpredictable pain). Dependent measures were self-reported fear and eyeblink startle. During acquisition, all groups received both predictable and unpredictable training. In the predictable context, one movement (CS+) was consistently followed by the shock-US, but another movement was not (CS−). In the unpredictable context, joystick movements never signaled the shock-US; shock-US were delivered during the intertrial interval (ITI). During extinction, the extinction group continued training in the predictable context but the CS+ movement was no longer reinforced; the context exposure group continued training in the unpredictable context but ITI shock-US were omitted. The control group continued training after the acquisition reinforcement scheme. Results revealed that fear ratings for the CS+ were extinguished in the extinction group but not in the control group. Interestingly, omitting the ITI shocks not only reduced ITI startle responses in the context exposure group compared with the control group, but also reduced the fear ratings and startle responses elicited by the unpredictable CS. The clinical implications of these findings are discussed.