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At least 307 records · Page 17Linked to original sources
PubMed2002

Neuroadaptive changes in NMDAR1 gene expression after extinction of cocaine self-administration.

The aim of the present work was to study the time course effects in levels of mRNA encoding N-methyl-d-aspartate receptor subunit 1 (NMDAR1) after long-term cocaine self-administration (1 mg/kg/ injection) and its extinction using a yoked-box procedure. NMDAR1 content was measured by quantitative in situ hybridization histochemistry in prefrontal cortex, caudate-putamen, nucleus accumbens, olfactory tubercle, and piriform cortex immediately after cessation of the last session of cocaine self-administration (Day 0) and 1, 5, and 10 days after the extinction period. The results show that long-term cocaine self-administration and its extinction alter NMDAR1 gene expression in these forebrain regions, and that the changes depend upon the brain region examined and the type of cocaine administration (contingent, noncontingent, and saline). Compared to saline and noncontingent cocaine administration, contingent cocaine produced an up-regulation in NMDAR1 gene expression on Day 0 in all the brain regions analyzed. NMDAR1 levels of contingent animals decreased progressively in the absence of cocaine, and the decrement persisted 10 days after the extinction of cocaine self-administration behavior in all the forebrain areas, with the exception of olfactory tubercle. In contrast, noncontingent cocaine administration did not produce any change in NMDAR1 gene expression on Day 0, and extinction resulted in an increase of NMDAR1 mRNA content on Days 1 and 5 and returned to control (saline) values on Day 10. These results suggest that an interaction between environmental stimuli and the pharmacological action of cocaine during drug self-administration and its extinction may represent an important factor in the regulation of cocaine effects on NMDAR1 gene expression.

Analysis of Variance↗
PubMed1994

Operant extinction in the treatment of severe maladaptive behavior: adapting research to practice.

Operant extinction involves termination of reinforcement for a previously reinforced response. As a clinical intervention for severe maladaptive behavior operant extinction is often repudiated because of intensity of side effects, length of treatment time required, and implementation difficulties. This article discusses both theoretical and practical aspects of extinction, including components of the extinction process and the importance of functional assessment to its effective use. Potential strategies for increasing the effectiveness of extinction while diminishing intrusiveness are recommended. Based on recent research innovations, a technology is emerging for effective use of operant extinction in the treatment of severe maladaptive behavior.

Adult↗
PubMed2006

Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes.

The interplay between fear expression and fear extinction provides an important prerequisite for adequate coping with aversive encounters. Current models propose that extinction of conditioned fear is mediated by associative safety learning. Here, we demonstrate that the cannabinoid CB1 receptor, which is crucially involved in fear extinction, is dispensable for associative safety learning. In fact, our results indicate that CB1 mediates fear extinction primarily via habituation-like processes. CB1 null-mutant mice were severely impaired not only in extinction of the fear response to a tone after fear conditioning but also in habituation of the fear response to a tone after sensitization with an inescapable footshock. Surprisingly, long-term habituation was generally affected even in situations with proper short-term adaptation, suggesting the existence of two separated CB1-dependent effector systems for short- and long-term fear adaptation. Our findings underscore the importance of habituation as a determinant of fear extinction in mice and characterize the cannabinoid CB1 receptor as an essential molecular correlate of this process.

Acoustic Stimulation↗
PubMed2006

Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice.

Extinction of conditioned fear responses is an active learning process resulting from the repeated presentation of a conditioned stimulus in the absence of the unconditioned aversive stimulus. Recent research implicates the medial prefrontal cortex (mPFC) in the mediation of fear extinction in rodents and the pathophysiology of posttraumatic stress disorder. However, there is currently little understanding of precisely how stress can impact fear extinction and the neural circuitry subserving this behavior. The present study examined the effects of brief exposure to an uncontrollable stressor on (1) fear conditioning and fear extinction, and (2) dendritic morphology of pyramidal neurons in the infralimbic (IL) and prelimbic (PL) regions of the mPFC in mice. Exposure to three episodes of stress ending 24 h before fear conditioning significantly attenuated the rate of cued fear extinction relative to nonstressed controls, but did not affect fear conditioning or cue or context recall. Analysis of Golgi-stained neurons showed that one or three exposures to daily swim stress caused significant retraction of terminal branches of apical, but not basilar, dendrites of IL neurons. In contrast, PL neuronal morphology was unaltered by stress. These data demonstrate that IL, but not PL, neurons are highly sensitive to even brief exposure to stress, and that this same form of stress impairs fear extinction. Present findings suggest that trauma may compromise the functional integrity of the mPFC with implications for the pathophysiology of certain neuropsychiatric disorders.

Animals↗
PubMed2006

Predicting extinctions as a result of climate change.

Widespread extinction is a predicted ecological consequence of global warming. Extinction risk under climate change scenarios is a function of distribution breadth. Focusing on trees and birds of the eastern United States, we used joint climate and environment models to examine fit and climate change vulnerability as a function of distribution breadth. We found that extinction vulnerability increases with decreasing distribution size. We also found that model fit decreases with decreasing distribution size, resulting in high prediction uncertainty among narrowly distributed species. High prediction uncertainty creates a conservation dilemma in that excluding these species under-predicts extinction risk and favors mistaken inaction on global warming. By contrast, including narrow endemics results in over-predicting extinction risk and promotes mistaken inaction on behalf of individual species prematurely considered doomed to extinction.

Animals↗
PubMed1993

Extinction of self-injurious escape behavior with and without instructional fading.

Three individuals with developmental disabilities participated in a study of the treatment of self-injurious behavior (SIB) maintained by negative reinforcement (escape from educational tasks). Treatment was implemented in a multiple baseline design across subjects, in which two treatments were compared in a multielement format. Both treatment conditions included an escape-extinction component in which SIB no longer produced escape. One of the conditions also included a fading component in which the frequency of instructions was initially reduced to zero and then was gradually faded back in across sessions until the instructional rate matched that of the original baseline. Results indicated that extinction alone reduced SIB to the end-of-treatment criterion in fewer sessions than did extinction plus fading for all 3 subjects. For 2 of the 3 subjects, however, there was an initial increase in the frequency of SIB at the outset of treatment with extinction (an extinction burst) that was not observed when extinction was combined with the fading component.

Adult↗
PubMed1999

Side effects of extinction: prevalence of bursting and aggression during the treatment of self-injurious behavior.

Findings from basic and applied research suggest that treatment with operant extinction may produce adverse side effects; two of these commonly noted are an increase in the frequency of the target response (extinction burst) and an increase in aggression (extinction-induced aggression). Although extinction is often used to treat problem behavior in clinical settings, few applied studies have examined the prevalence of these side effects or their possible attenuation with other operant procedures. An analysis of 41 data sets for individuals who received treatment for self-injurious behavior indicated that extinction bursts or increases in aggression occurred in nearly one half of the cases. The prevalence of bursting and aggression was substantially lower when extinction was implemented as part of a treatment package rather than as the sole intervention.

Adult↗
PubMed2004

Enhancing the effects of extinction on attention-maintained behavior through noncontingent delivery of attention or stimuli identified via a competing stimulus assessment.

UNLABELLED: Recent research has shown that the noncontingent delivery of competing stimuli can effectively reduce rates of destructive behavior maintained by social-positive reinforcement, even when the contingency for destructive behavior remains intact. It may be useful, therefore, to have a systematic means for predicting which reinforcers do and do not compete successfully with the reinforcer that is maintaining destructive behavior. In the present study, we conducted a brief competing stimulus assessment in which noncontingent access to a variety of tangible stimuli (one toy per trial) was superimposed on a fixed-ratio 1 schedule of attention for destructive behavior for individuals whose behavior was found to be reinforced by attention during a functional analysis. Tangible stimuli that resulted in the lowest rates of destructive behavior and highest percentages of engagement during the competing stimulus assessment were subsequently used in a noncontingent tangible items plus extinction treatment package and were compared to noncontingent attention plus extinction and extinction alone. Results indicated that both treatments resulted in greater reductions in the target behavior than did extinction alone and suggested that the competing stimulus assessment may be helpful in predicting stimuli that can enhance the effects of extinction when noncontingent attention is unavailable. DESCRIPTORS: Attention-maintained problem behavior, competing stimuli, extinction, functional analysis, noncontingent reinforcement

Attention Deficit Disorder with Hyperactivity↗
PubMed1975

Frequency of reinforcement as a determinant of extinction-induced aggression during errorless discrimination learning.

Seven pigeons were trained to discriminate without errors between a green keylight and a dark key. The key-pecking response was reinforced in the presence of green, and extinction was in effect in the presence of the dark key. The opportunity to attack a restrained target pigeon was present only during extinction. Both variable-interval 30-sec and fixed-ratio 1 schedules of reinforcement during the positive stimulus induced a higher rate of attack during extinction than a variable-interval 5-min schedule. The highest rate of attack during extinction occurred during the first 20 sec after the positive stimulus terminated. Hence, the withdrawal of the positive condition, rather than the consequences of the pecking response during extinction, appears to be one of the primary factors responsible for attack between pigeons during extinction. Behavioral contrast, defined as a decrease in the rate of responding when the positive stimulus was presented alone, was obtained from the four birds that displayed the lowest overall rates of attack while the three birds with the highest attack rates did not display behavioral contrast. For the birds without contrast, components of the attack response during the positive stimulus presumably competed with and reduced the rate of pecking the key, thereby recluding behavioral contrast.

Aggression↗
PubMed2001

Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration.

Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylase (TH) levels in the mesolimbic dopamine system. In this study, 12 d of cocaine self-administration in rats (4 hr/d) reduced TH immunoreactivity by 29% in the nucleus accumbens (NAc) shell, but not core, after a 1 week withdrawal period. In contrast, TH immunoreactivity in the NAc was completely restored in animals that experienced extinction training (4 hr/d) during the same withdrawal period. Extinction training also increased TH levels in the ventral tegmental area (VTA) by 45%, whereas TH was not altered in the VTA by cocaine withdrawal alone. Thus, extinction-induced normalization of NAc TH levels could involve increased TH synthesis, stability, and/or transport from the VTA to the NAc. A similar extinction training regimen failed to alter TH levels in the NAc or VTA of rats trained to self-administer sucrose pellets, indicating that TH regulation in cocaine-trained animals is not a generalized effect of extinction learning per se. Rather, these data suggest that neuroadaptative responses during cocaine withdrawal ultimately are determined by a complex interaction between chronic drug exposure and drug-seeking experience. The ability of extinction training to restore NAc TH levels is hypothesized to accelerate recovery from dopamine depletion and anhedonia during cocaine withdrawal.

Animals↗
PubMed2002

Effects of extinction context and retrieval cues on alcohol cue reactivity among nonalcoholic drinkers.

Pavlovian conditioning models have influenced the development of cue exposure treatments for drug abuse. However, poor maintenance of extinction performance (renewal) after treatment is a common problem. A treatment-analogue experiment tested the role of context in renewal, as well as a potential strategy for reducing renewal. Seventy-eight social drinkers completed extinction trials to reduce saliva and urge reactivity to alcohol cues and were randomly assigned to a renewal test in either the same context as extinction, a different context, or the different context containing a cue from the extinction context (E-cue). As predicted, the different context produced greater renewal than the same context and renewal was attenuated when the E-cue was present. These results offer preliminary evidence for the context dependence of extinction to alcohol cues and for the use of an extinction cue to improve the generalizability of exposure therapies.

Adolescent↗
PubMed2003

Identification of calcineurin as a key signal in the extinction of fear memory.

Memory extinction refers to a gradual decrease of the previously acquired response when exposed to conditional stimulus without pairing with unconditional stimulus. Here we show for the first time that fear training-induced phosphorylation of specific substrates in the rat amygdala is reduced after extinction trials and is accompanied by an increase in the protein level and enzymatic activity of calcineurin. In parallel, calcineurin inhibitors prevented extinction-induced protein dephosphorylation as well as extinction of fear memory. Thus, extinction training increased phosphatase activity likely via an expression of calcineurin. Calcineurin then created a negative-feedback loop and directly or indirectly dephosphorylated specific substrates, which, in their phosphorylated state, were required for memory consolidation. Accordingly, in our experimental condition, extinction could be ascribed at least in part to a weakening of the original signaling.

Amygdala↗
PubMed2006

[Influence of activation and blockade of NMDA receptors on extinction of passive avoidance response in mice with different levels of anxiety].

Influence of agonist (D-cycloserine) and antagonist (dizocilpine) N-methyl-D-aspartate receptors on learning and extinction of passive avoidance response in medium-, high-, and low-anxious mice was studied. In medium-anxious mice, D-cycloserine (30 mg/kg) although not changing learning accelerated development of extinction, whereas dizocilpine (0.15 mg/kg), while impairing passive avoidance learning, detained the extinction. In high-anxious mice with good retrieval of memory trace and absence of extinction, D-cycloserine was ineffective, whereas dizocilpine reduced learning and promoted retention of memory trace retrieval at the generated level on extinction. In low-anxious mice, D-cycloserine impaired learning and accelerated extinction, whereas dizocilpine completely blocked learning and retention of passive avoidance response.

Animals↗
PubMed1984

Acquisition and extinction of conditioned suppression of a graft-vs-host response in the rat.

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution results in a conditioned aversion to saccharin and a conditioned suppression of immune responses. In this study, female Lewis X Brown Norwegian F1 rats were conditioned by pairing saccharin with 50 mg/kg CY. Seven weeks later (day 0), a graft-vs-host response (GvHR) was induced in these animals by injecting splenic leukocytes from Lewis donors into a rear footpad. At this time, some conditioned animals were reexposed to saccharin, the conditioned stimulus. During the 7-wk interval between conditioning and immunization, subgroups of conditioned rats were given 0, 4, 9, or 18 extinction trials (saccharin followed by saline injections). Animals receiving 4, 9, or 18 extinction trials showed a greater preference for saccharin on day 0 than did animals receiving no extinction trials, but these groups did not differ among themselves; all conditioned groups showed a lower preference for saccharin than placebo-treated animals. There was a clear effect of number of extinction trials on the GvHR. Animals receiving 9 or 18 extinction trials did not differ from controls, whereas animals receiving 0 or 4 trials had a milder GvHR than did conditioned rats that were not reexposed to saccharin at the time of immunization. These results confirm a previous report of conditioned suppression of a GvHR, demonstrate that conditioned immunopharmacologic responses are subject to experimental extinction, and indicate that conditioned immunosuppression can be dissociated from conditioned taste aversion.

Animals↗
PubMedDate not supplied

[Effect of mammillary body ablation on extinctive inhibition in cats].

Chronic extinction of chain closed conditioned reflex in intact rabbits took five to six days. The order of extinction of the reflex links was as follows: the nearer to reinforcement the link of the chain, the sooner it was inhibited. In the course of extinction different "compensatory" movements appeared with a high frequency. Unlike the conditioned movements they were not fully extinguished: in the rest periods (lying for 4 to 10 min.), running and sniffing took place 4 to 8 times in the session. After the ablation of the mammilary bodies, extinctive inhibition was developing slower (9 to 13 days) than in the norm. The order of extinction became reverse: the nearer the link of the chain to reinforcement, the greater the difficulty of inhibition. The appearance of "compensatory" movements sharply differed from the norm. The general behaviour of the operated rabbits was peculiar in that during extinction of conditioned movements the short periods of rest (1 to 3 min.) alternated with running, sitting, scratching, washing, etc.

Animals↗
PubMed1998

Extinction in fear conditioning: effects on startle modulation and evaluative self-reports.

A basic feature of human evaluative conditioning is that the reported acquired valence of a previously neutral conditioned stimulus (CS) that has been paired with a valenced unconditioned stimulus (US), is resistant to extinction. The present study investigated whether startle modulation, sometimes presented as an index of acquired valence, reflected this basic feature. In a differential fear conditioning paradigm (n = 38) with an electrocutaneous stimulus as the US, a strong extinction manipulation was conducted by removing the US-electrodes and by extended extinction trials. At the end of extinction, the results corroborated previous findings of evaluative conditioning in that the reported valence for CS+ was still more negative than for CS-, despite disappearance of the differential skin conductance responses. However, startle modulation did not show resistance-to-extinction. Results were discussed in terms of recent conceptualizations of extinction.

Adolescent↗
PubMed2000

Extinction.

In the life of any species, extinction is the final evolutionary process. It is a common one at present, as the world is entering a major extinction crisis. The pattern of extinction and threat is very non-random, with some taxa being more vulnerable than others. Explaining why some taxa are affected and some escape is a major goal of conservation biology. More ambitiously, a predictive model could, in principle, be built by integrating comparable studies of past and present extinctions. We review progress towards both explanatory and predictive frameworks, comparing correlates of extinction in different groups at different times. Progress towards explanatory models for the current crisis is promising, at least in some well-studied taxa, but the development of a truly predictive model is hampered by the formidable difficulties of integrating studies of present and past extinctions.

Animals↗
PubMed2000

Population extinction and quasi-stationary behavior in stochastic density-dependent structured models.

Density-independent and density-dependent, stochastic and deterministic, discrete-time, structured models are formulated, analysed and numerically simulated. A special case of the deterministic, density-independent, structured model is the well-known Leslie age-structured model. The stochastic, density-independent model is a multitype branching process. A review of linear, density-independent models is given first, then nonlinear, density-dependent models are discussed. In the linear, density-independent structured models, transitions between states are independent of time and state. Population extinction is determined by the dominant eigenvalue lambda of the transition matrix. If lambda < or = 1, then extinction occurs with probability one in the stochastic and deterministic models. However, if lambda > 1, then the deterministic model has exponential growth, but in the stochastic model there is a positive probability of extinction which depends on the fixed point of the system of probability generating functions. The linear, density-independent, stochastic model is generalized to a nonlinear, density-dependent one. The dependence on state is in terms of a weighted total population size. It is shown for small initial population sizes that the density-dependent, stochastic model can be approximated by the density-independent, stochastic model and thus, the extinction behavior exhibited by the linear model occurs in the nonlinear model. In the deterministic models there is a unique stable equilibrium. Given the population does not go extinct, it is shown that the stochastic model has a quasi-stationary distribution with mean close to the stable equilibrium, provided the population size is sufficiently large. For small values of the population size, complete extinction can be observed in the simulations. However, the persistence time increases rapidly with the population size.

Age Factors↗