Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “extinction”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1996

The NMDA antagonist MK-801 blocks the extinction of Pavlovian fear conditioning.

Five groups of rats were given Pavlovian fear conditioning. Four groups were then given extinction training. Prior to extinction these groups received an injection of either the noncompetitive NMDA antagonist MK-801 (0.025, 0.05, or 0.1 mg/kg) or saline. The 5th group received saline but no extinction. During testing, the extinction groups given saline or 0.025 mg/kg of MK-801 showed reduced fear, but the groups that had received the higher doses exhibited as much conditioned fear as the saline group, which had not received extinction. This study showed that MK-801 blocked extinction in a dose-dependent manner. The design of the study ruled out the possibility that the effect was due to state-dependency or to MK-801 interfering with the processing of the conditioned stimulus.

Animals↗
PubMed2004

Temporal specificity of extinction in autoshaping.

Three experiments investigated the effects of varying the conditioned stimulus (CS) duration between training and extinction. Ring doves (Streptopelia risoria) were autoshaped on a fixed CS-unconditioned stimulus (US) interval and extinguished with CS presentations that were longer, shorter, or the same as the training duration. During a subsequent test session, the training CS duration was reintroduced. Results suggest that the cessation of responding during an extinction session is controlled by generalization of excitation between the training and extinction CSs and by the number of nonreinforced CS presentations. Transfer of extinction to the training CS is controlled by the similarity between the extinction and training CSs. Extinction learning is temporally specific.

Animals↗
PubMed2005

Resistance to extinction in the steady state and in transition.

Three experiments with pigeons explored the constancy of reinforcer omission during extinction conjectured by rate estimation theory. Experiment 1 arranged 3-component multiple variable-interval (VI) schedules with a mixture of food and extinction trials within each session. Reinforcers omitted to an extinction criterion increased with food-trial reinforcer rate. Experiment 2 arranged 3-component multiple VI schedules where components differed in rate or number of reinforcers. Resistance to extinction depended on the training reinforcer rate but not on the number of reinforcers omitted. Experiment 3 replicated the partial-reinforcement extinction effect within subjects in a discrete-trial procedure and found that more reinforcers were omitted in continuous- than in partial-reinforcement trials. A model of extinction based on behavioral momentum theory accounted for all the data.

Animals↗
PubMed2003

Effects of D-cycloserine on extinction of conditioned freezing.

The present study tested the prediction that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, would facilitate extinction of conditioned freezing in male Sprague-Dawley rats. Rats received 5 light-shock pairings (conditioning). The following day, rats received 6 light-alone presentations (extinction training). Twenty-four hours later, rats received 1 light-alone presentation (test). Subcutaneous DCS injection before or after extinction training significantly enhanced extinction, and the dose-response curve for this effect was linear. Increasing the delay of DCS administration after extinction training led to a linear decrease in the facilitatory effect. The effect of systemic administration was replicated by intra-basolateral amygdala infusion. These results suggest that DCS facilitates extinction of conditioned freezing by acting on consolidation processes partly mediated by the basolateral amygdala.

Amygdala↗
PubMed1976

Hormonal influences on sexual dimorphism in rate of extinction of a conditioned taste aversion in rats.

The hormonal influences on the slow extinction rate of a conditioned taste aversion shown by male rats and the fast extinction rate shown by female rats were investigated. When males were castrated, they extinguished as quickly as females. When castrated males were given testosterone propionate replacement, they had a slow extinction rate. Castration had no effect on the extinction rate of females. But when testosterone propionate was administered to castrated or intact females, they had a slow, malelike extinction rate. Thus, sexual dimorphism in the extinction rate of a conditioned taste aversion seems to be due to the activational effects of testosterone.

Animals↗
PubMed2004

Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value.

In extinction, an animal learns that a previously conditioned stimulus (CS+) no longer predicts delivery of a salient reinforcer (unconditioned stimulus, UCS). Rodent studies indicate that extinction relies on amygdala-prefrontal interactions and involves formation of memories that inhibit, without actually erasing, the original conditioning trace. Whether extinction learning in humans follows similar neurobiological principles is unknown. We used functional magnetic resonance imaging to measure human brain activity evoked during olfactory aversive conditioning and extinction learning. Neural responses in orbitofrontal cortex and amygdala were preferentially enhanced during extinction, suggesting potential cross-species preservation of learning mechanisms that oppose conditioning. Moreover, by manipulating UCS aversiveness via reinforcer inflation, we showed that a CS+ retains access to representations of UCS value in distinct regions of ventral prefrontal cortex, even as extinction proceeds.

Adolescent↗
PubMed2006

Glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction of conditioned fear in rats.

Recent results show that brain glucocorticoids are involved in the dysregulation of fear memory extinction in post-traumatic stress disorder patients. The present study was aimed to elucidate the possible mechanism of glucocorticoids on the conditioned fear extinction. To achieve these goals, male SD rats, fear-potentiated startle paradigm, and Western blot were used. We found that (1) systemic administration of the synthetic glucocorticoid agonist dexamethasone (DEX) facilitated extinction of conditioned fear in a dose-dependent manner (0.05, 0.1, 0.5, or 1.0 mg/kg, i.p.); (2) systemic administration of the glutamate NMDA receptor antagonist (+/-)-HA966 (6.0 mg/kg, i.p.) and intra-amygdala infusion of the NMDA receptor antagonists MK801 (0.5 ng/side, bilaterally) or D,L-2-amino-5-phosphonovaleric acid (AP5, 2.0 ng/side, bilaterally) blocked the DEX facilitation effect; (3) the corticosteroid synthesis inhibitor metyrapone (25 mg/kg. s.c.) blocked extinction and this was prevented by co-administration of NMDA receptor agonist D-cycloserine (DCS, 5.0 mg/kg, i.p.); (4) co-administration of DEX and DCS in subthreshold doses provided a synergistic facilitation effect on extinction (0.2 and 5 mg/kg, respectively). Control experiments indicated that co-administration of DEX and DCS did not alter the expression of conditioned fear and the effect was not due to lasting damage to the amygdala. These results suggest that glutamate NMDA receptors within the amygdala participate in the modulatory effect of glucocorticoids on extinction.

Amygdala↗
PubMed2003

Systemic or intra-amygdala injections of glucose facilitate memory consolidation for extinction of drug-induced conditioned reward.

The conditioned place preference (CPP) task has been used extensively to investigate the neurobiological bases of drug-induced reward. The initial expression of a CPP involves memory for an association between environmental stimuli and the affective state produced by a rewarding treatment. The present experiments examined the hypothesis that post-trial administration of glucose can facilitate memory consolidation processes underlying the extinction of drug-induced CPP behaviour. Adult male Long-Evans rats acquired an amphetamine CPP, and subsequently received extinction training. Immediately following extinction training, separate groups of rats received peripheral (100 mg/kg, 500 mg/kg, or 2 g/kg) or intra-amygdala (basolateral nucleus; 1.5 micro g/0.5 micro L or 10 micro g/0.5 micro L) injections of glucose or vehicle. Peripheral (100 mg/kg and 2 g/kg) and intra-amygdala (1.5 and 10 micro g) glucose injections facilitated the extinction of amphetamine CPP behaviour relative to vehicle-injected controls. Postextinction trial peripheral or intra amygdala glucose injections that were delayed 2 h had no effect. The findings indicate that: (i) extinction of approach behaviour to drug-associated cues involves the formation of new memories that undergo a time-dependent consolidation process; and (ii), systemic or intra-amygdala administration of a known memory-enhancing agent facilitates extinction of drug-induced CPP behaviour.

Amphetamine↗
PubMed2002

Active tool use with the contralesional hand can reduce cross-modal extinction of touch on that hand.

After a unilateral brain lesion, patients may show cross-modal, visual-tactile extinction. Such patients may fail to report tactile stimuli on the contralesional hand when presented together with competing visual stimuli near the ipsilesional hand. In this work we tested the hypothesis that this cross-modal extinction may be reduced when a patient has used a tool with the contralesional hand to reach for objects in the ipsilesional visual field. Consistent with previous work, we hypothesize that active use of a tool may extend cross-modal interactions between visual stimuli at the tip of the tool and tactile stimuli on the hand wielding the tool. In the new situation of a tool connecting the contralesional hand with ipsilesional visual space, competition between stimuli on these opposite sides may be reduced, so that extinction decreases. We studied patient BV, who showed reliable cross-modal, visual-tactile extinction after right-hemisphere stroke. In two separate sessions we showed that prolonged tool use (10-20 min) with the contralesional hand in ipsilesional space reduced cross-modal extinction for up to 60-90 min post-training. We propose that an actively used tool may be effective in linking cross-modal stimuli presented along its extension. This can then overcome competition between stimuli presented on opposite sides of the body midline, thus modulating extinction.

Aged↗
PubMed1988

Different mechanisms of ipsilateral and contralateral ear extinction in aphasic patients.

Dichotic listening performance was studied in 35 aphasic patients with unilateral brain lesions. Within this group, 30 patients exhibited an abnormal ear discrepancy: 20 patients showed a left-ear advantage (right-ear extinction), and 10 patients showed a right-ear advantage (left-ear extinction). All subjects were given a number of verbal tasks in order to evaluate several aspects of their linguistic abilities. For the left-ear advantage group, verbal scores were positively related to left-ear scores, but not to right-ear scores. For the right-ear advantage group, verbal scores were positively related to both left- and right-ear scores. The present results lend partial support for the prediction that right-ear extinction is associated with damage to the temporal lobe involving the geniculo-temporal system. No support was found for the prediction that left-ear extinction is associated with lesions placed in the deep structures of the parietal or parieto-occipital lobe involving the corpus callosum system. Our data indicate that the initial severity of brain injury is a critical factor in determining the direction of ear extinction, the lesions being larger in the left-ear advantage group. Results are discussed in relationship to other explanations of ipsilateral and contralateral extinction in aphasic patients.

Adult↗
PubMed1999

Effects of lithium dose (UCS) on the acquisition and extinction of a discriminated morphine aversion: tests with morphine and delta9-THC.

The effects of varying the lithium dose (unconditioned stimulus [UCS]; LiCl range 30-180 mg/kg) on the acquisition and extinction of stimulus control by 5.6 mg/kg of morphine in a discriminated taste aversion (DTA) procedure were examined in rats. In addition, pharmacological specificity was examined by substituting (-)-delta-9-tetrahydrocannabinol (delta9-THC) for morphine during a test phase intervening between acquisition and extinction. DTA acquisition was more rapid at higher LiCl doses. The lowest dose of LiCl, 30 mg/kg, did not robustly maintain a DTA. Two groups treated with 60 mg/kg LiCl, differing only in the type of drinking nozzle used (ball-bearing vs standard non-ball-bearing), behaved similarly. Suppression of drinking was related to the morphine dose, in an orderly manner (dose range 0.3-10 mg/kg), in rats for which morphine was followed by LiCl. No significant decline in drinking occurred for rats for which morphine was followed by saline, except perhaps at the 10 mg/kg test dose of morphine. The control of drinking was pharmacologically specific; both experimental and control animals were equally affected in tests with delta9-THC (0.3-10 mg/kg). Low doses of delta9-THC increased water consumption; this did not occur with morphine. During extinction the reinstitution of drinking was similar across groups that had been effectively conditioned, i.e. there was no apparent effect of lithium dose on extinction. After extinction, a much attenuated reaction occurred to morphine in tests with 3 and 10 mg/kg. These doses of morphine had significantly suppressed drinking before the extinction phase. Collectively, these data add to the formal similarities between sensory and drug discriminative stimuli.

Animals↗
PubMed2002

Reinstatement and spontaneous recovery of cocaine-seeking following extinction and different durations of withdrawal.

Stimuli paired with drug use can acquire powerful motivational properties that are believed to induce relapse to drug-seeking in abstinent humans. Behavioural interventions for drug addiction, that have attempted to reduce the probability of relapse by extinguishing the motivational impact of drug-associated conditioned stimuli (CS), have had limited success. One explanation for the ready propensity to relapse to drug-seeking even following extinction of these stimuli may be that abstinence by humans can increase the ability of conditioned stimuli and drug primes to reinstate responding. In the present study, we sought to determine the effects on cocaine-seeking of imposing different periods of drug unavailability on rats, with or without extinction of the drug-seeking response and non-reinforced exposure to drug-associated stimuli. Rats were trained to self-administer cocaine under a second-order schedule of reinforcement, under which high response rates are maintained by drug-paired conditioned reinforcers, prior to extinction of the operant response alone or in combination with contingent presentation of the CS. Comparison of cocaine-seeking behaviour during a test session conducted either 1 day or 21 days after a 7-day period of extinction revealed that responding was significantly decreased the day after extinction, but spontaneously recovered following a further imposed period of 21 days during which cocaine and cocaine cues were not available. Self-administered cocaine further potentiated reinstated responding following all withdrawal periods. These findings are discussed with reference to interactions between drug unavailability, conditioned stimuli and cocaine self-administration, on the reinstatement of drug-seeking and the potential utility of extinction therapies for drug addiction.

Animals↗
PubMedDate not supplied

Extinction learning before trauma and subsequent posttraumatic stress.

OBJECTIVE: Fear conditioning theories propose that persistent stress reactions may occur as a result of impaired extinction learning, and a poor capacity for extinction learning may predispose some individuals to posttraumatic stress disorder development. This study indexed the extent to which deficits in extinction learning before trauma exposure are a risk factor for persistent posttraumatic stress after trauma exposure. METHODS: Eighty-four firefighters were assessed during cadet training (before trauma) and 70 were reassessed within 24 months of commencing active firefighting duties (after trauma). Measures of posttraumatic stress were used before and after trauma exposure. In addition, skin conductance and corrugator electromyogram (EMG) responses were obtained during fear conditioning and extinction paradigms before trauma exposure. RESULTS: Reduced extinction of an aversively conditioned corrugator EMG response pretrauma predicted 31% of the variance in posttraumatic stress severity. CONCLUSIONS: This result provides preliminary support for reduced extinction of a conditioned emotional response as a vulnerability factor for posttraumatic stress.

Adult↗
PubMed2006

Prefrontal dopamine D4 receptors are involved in encoding fear extinction.

The medial prefrontal cortex is known to be crucially involved in the memory for fear extinction. It has been shown that the dopamine D4 receptor is abundantly localized in the medial prefrontal cortex of rodents and that this receptor subtype is involved in the mediation of fear-related behaviour. In the present study, we tested whether dopamine D4 receptors within the medial prefrontal cortex are involved in the learning and encoding of fear extinction. Infusions of the specific dopamine D4 receptor antagonist L-741,741 into the medial prefrontal cortex immediately before fear extinction did not affect fear extinction learning but attenuated the memory on fear extinction on the following day. These results suggest that medial prefrontal cortex dopamine D4 receptors are involved in the consolidation of fear extinction memory.

Animals↗
PubMed2006

A role for hippocampal gastrin-releasing peptide receptors in extinction of aversive memory.

Although the gastrin-releasing peptide receptor has been implicated in memory consolidation, previous studies have not examined whether it is involved in extinction. Here we show that gastrin-releasing peptide receptor blockade in the hippocampus disrupts extinction of aversive memory. Male rats were trained in inhibitory avoidance conditioning and then returned repeatedly to the training context without shock on a daily basis for 3 days. Infusion of a gastrin-releasing peptide receptor antagonist or the protein synthesis inhibitor anisomycin into the dorsal hippocampus immediately after the first extinction session blocked extinction. These drugs did not affect performance in subsequent sessions when the first extinction session (1 day after training) was omitted. The results indicate that hippocampal gastrin-releasing peptide receptors are involved in memory extinction.

Animals↗
PubMedDate not supplied

Purkinje cell loss by OX7-saporin impairs acquisition and extinction of eyeblink conditioning.

The current study examined the effects of globally depleting Purkinje cells in the cerebellar cortex with the immunotoxin OX7-saporin on acquisition and extinction of delay eyeblink conditioning in rats. Rats were given OX7-saporin or saline 2 wk before the start of eyeblink conditioning. The rats that reached a performance criterion of two consecutive days with 80% or greater conditioned responses were given 5 d of extinction training followed by 2 d of reacquisition training. Rats that received infusions of OX7-saporin had 77.2%-97.9% Purkinje cell loss and exhibited impaired acquisition and extinction. The amount of Purkinje cell loss was correlated with the magnitude of the acquisition and extinction impairments. The highest correlations between Purkinje cell number and the rate of acquisition were in lobule HVI and the anterior lobe. The highest negative correlation between Purkinje cell number and the percentage of conditioned responses during extinction was in the anterior lobe. The results indicate that cerebellar Purkinje cells, particularly in the anterior lobe and lobule HVI, play significant roles in acquisition and extinction of eyeblink conditioning.

Analysis of Variance↗
PubMedDate not supplied

Extinction memory improvement by the metabolic enhancer methylene blue.

We investigated whether postextinction administration of methylene blue (MB) could enhance retention of an extinguished conditioned response. MB is a redox compound that at low doses elevates cytochrome oxidase activity, thereby improving brain energy production. Saline or MB (4 mg/kg intraperitoneally) were administered to rats for 5 d following extinction training of tone-footshock conditioning. Postextinction freezing was lower in rats receiving MB compared with saline, suggesting that MB improved retention of the extinction memory. The MB effect was specific to tone-evoked freezing because there were no differences in pretone freezing. Control subjects similarly injected with MB showed no evidence of nonspecific effects on measures of motor activity and fearfulness. MB-treated rats exhibited both greater retention of extinction and greater overall brain metabolic activity. Rats with higher retention of extinction also showed a relative increase in cytochrome oxidase activity in prefrontal cortical regions, especially anterior infralimbic cortex, dorsal and medial frontal cortex, and lateral orbital cortex. These regional metabolic increases were also correlated to the behavioral freezing index used to assess retention of extinction. It was concluded that MB administered postextinction could enhance retention of extinction memory through an increase in brain cytochrome oxidase activity.

Animals↗
PubMed2006

The role of the basolateral amygdala in stimulus-reward memory and extinction memory consolidation and in subsequent conditioned cued reinstatement of cocaine seeking.

The consolidation of cue-cocaine associations and extinction learning (i.e. cue-no cocaine associations) into long-term memory probably regulates the long-lasting control of conditioned stimuli (CS) over cocaine-seeking behaviour, and the basolateral amygdala (BLA) may play a role in this phenomenon. To test this hypothesis, rats previously trained to self-administer cocaine underwent a single classical conditioning (CC) session, during which they received passive pairings of cocaine infusions and a novel light + tone stimulus complex. After additional self-administration sessions in the absence of CS presentation and subsequent extinction training sessions, the ability of the CS to reinstate cocaine-seeking on five test days was assessed. Rats received intra-BLA microinfusions of vehicle or the Na+-channel blocker tetrodotoxin (TTX) immediately after CC (consolidation of CS-cocaine associations) or immediately after reinstatement testing (consolidation of extinction learning). TTX administered immediately after CC attenuated subsequent CS-induced reinstatement. In contrast, TTX administered after the first reinstatement test impaired the extinction of cocaine-seeking behaviour during a second reinstatement test by disrupting extinction memory. Overall, these findings suggest that Na+ channel-mediated mechanisms within the BLA mediate the consolidation of both cocaine-stimulus association and extinction learning, two processes that have opposite effects on subsequent cue-induced cocaine-seeking behaviour.

Amygdala↗