The effect of yohimbine on the extinction of conditioned fear: A role for context.

Six experiments with rat subjects examined the effect of yohimbine, an alpha-2 adrenergic autoreceptor antagonist, on the extinction of conditioned fear to a tone. Experiments 1 and 2 demonstrated that systemic administration of yohimbine (1.0 mg/kg) facilitated a long-term decrease in freezing after extinction, and this depended on pairing drug administration with extinction training. However, Experiments 3 and 4 demonstrated that yohimbine did not eradicate the original fear learning: Freezing was renewed when the tone was tested outside of the extinction context. Experiments 5 and 6 found that the contextually specific attenuation of fear produced by yohimbine transferred to another extinguished conditional stimulus (CS) and not to a nonextinguished CS. The results suggest that yohimbine, when administered in the presence of a neutral context, creates a form of inhibition in that context that allows that specific context to reduce fear of an extinguished CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Expression of renewal is dependent on the extinction-test interval rather than the acquisition-extinction interval.

A recent finding suggested that when extinction occurs shortly after acquisition, renewal of an extinguished fear response (fear-potentiated startle) to a light conditioned stimulus (CS) is diminished (Myers, Ressler, & Davis, 2006). The present study attempted to extend this finding using a white-noise CS and freezing as the behavioral measure of fear. In Experiments 1A and 1B, we observed renewal whether extinction occurred 10 min or 24 hr after acquisition. In contrast, renewal was not observed if test occurred 10 min after extinction (Experiment 2). Experiment 3 demonstrated that expression of extinction at the 10-min extinction-test interval was attenuated by a pretest subcutaneous injection of the γ-aminobutyric acid (GABA) inverse agonist FG7142. These findings suggest that renewal is influenced more by the extinction-test interval than the acquisition-extinction interval. Further, the failure to see renewal 10 min after extinction suggests that there is a separate context memory that undergoes a different consolidation function than the CS-no US memory formed during extinction. Finally, the expression of extinction appears to be GABA dependent regardless of the extinction-test interval or the test context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A short intertrial interval facilitates acquisition of context-conditioned fear and a short retention interval facilitates its expression.

Rats were shocked in a context on two occasions and then tested for fear reactions as indexed by freezing. Rats spent the interval between conditioning trials and between conditioning and test in their home cages. A short interval between context-conditioning trials or between trials involving a discrete conditioned stimulus (CS) produced better learning than longer intervals. A short retention interval between conditioning and test produced better performance than longer intervals. The effects of the intertrial interval on learning are the opposite of those reported previously and are opposite to those predicted by contemporary learning theories. The effects of the training to test interval on performance are predicted by Wagner's sometimes opponent process (SOP) theory (Wagner, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous recovery of extinguished fear responses deepens their extinction: A role for error-correction mechanisms.

A series of experiments used a within-subject design to study spontaneous recovery of fear responses (freezing) to an extinguished conditioned stimulus (CS) in rats. Experiments 1, 2, 3, and 4 demonstrated that: a remotely extinguished CS elicited more freezing than a recently extinguished one on a common test; that the CS showing recovery underwent greater response loss across additional extinction than the one lacking recovery; and that spontaneous recovery and deepening of response loss survived reconditioning. Experiment 5 demonstrated that an excitor extinguished in compound with a CS showing recovery suffered greater loss than an excitor extinguished in compound with a CS not showing recovery, implying that the differential change is regulated by a common error term. Experiments 6 and 7 demonstrated that extinction of a compound composed of two CSs, one showing recovery and a second lacking recovery, produced greater loss to the CS that showed recovery, implying that the change is also regulated by individual error term. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of extinguished fear by β-adrenergic arousal elicited by a conditioned context.

Five experiments examined the reinstatement of fear (freezing) produced by recent reexposure to a dangerous context. Rats were trained to fear a conditioned stimulus (CS) and a distinctive context with shock. The CS was then extinguished. A 2-min interval between reexposure to the dangerous context and presentation of the extinguished CS in a different context reinstated freezing when the CS was tested the next day. Propranolol (a β-adrenergic antagonist) blocked reinstatement of extinguished fear without decreasing freezing to a nonextinguished CS. Administration of epinephrine (an adrenergic agonist) reinstated extinguished fear without reexposure to the dangerous context. The results suggest a role for β-adrenergic activity elicited by exposure to a conditioned context in the reinstatement of extinguished fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Massed extinction trials produce better short-term but worse long-term loss of context conditioned fear responses than spaced trials.

A series of experiments studied the effects of the interval between extinction trials on the loss of context conditioned freezing responses. Rats were shocked in one context (A) but not in another (B) and subjected to extinction trials in context A. In Experiment 1, massed trials produced more rapid loss than spaced trials. A shift from spaced to massed trials maintained this loss, but the shift from massed to spaced trials restored lost responses. Experiments 2-5 examined this effect of massed trials on responding across spaced trials. They provided evidence that (a) a single trial was as effective as multiple daily massed trials, (b) learning occurred on the first of the massed trials but not on later ones, and (c) the first trial reduced the amount learned across subsequent massed trials. Finally, alternating extinction trials in A and B produced more response loss across spaced trials than blocks of trials in A and B. The results were discussed in terms of the role accorded to self-generated priming in the models developed by A. R. Wagner (1978, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual control over conditioned responding in an extinction paradigm.

Four experiments studied contextual control over rats' freezing to conditioned stimuli (CSs) that had been paired with shock and were then extinguished. In Experiment 1, rats were exposed to a CS A–shock and a CS B–shock pairing in Context C. CS A was then extinguished in Context A, and CS B in Context B. Freezing was renewed when each CS was presented in the context where the other CS had been extinguished. In Experiments 2–4, rats were exposed to a CS A–shock pairing in A and a CS B–shock pairing in B. They were then exposed to Context C where one, both, or neither of the CSs were extinguished, or where both CSs continued to be reinforced. On test, the rats froze more to CS A than to CS B in Context A, and more to CS B than to CS A in Context B, but only if the CSs had been extinguished. Thus, after extinction, rats use contexts to regulate retrieval not only of their memory for extinction, but also of their memory for the original conditioning episode. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous recovery but not reinstatement of the extinguished conditioned eyeblink response in the rat.

Reinstatement—the return of an extinguished conditioned response (CR) after reexposure to the unconditioned stimulus (US)—and spontaneous recovery—the return of an extinguished CR with the passage of time—are 2 of 4 well-established phenomena that demonstrate that extinction does not erase the conditioned stimulus (CS)–US association. However, reinstatement of extinguished eyeblink CRs has never been demonstrated, and spontaneous recovery of extinguished eyeblink CRs has not been systematically demonstrated in rodent eyeblink conditioning. In Experiment 1, US reexposure was administered 24 hr prior to a reinstatement test. In Experiment 2, US reexposure was administered 5 min prior to a reinstatement test. In Experiment 3, a long, discrete cue (a houselight), present in all phases of training and testing, served as a context within which each trial occurred to maximize context processing, which in other preparations has been shown to be required for reinstatement. In Experiment 4, an additional group was included that received footshock exposure, rather than US reexposure, between extinction and test, and contextual freezing was measured prior to test. Spontaneous recovery was robust in Experiments 3 and 4. In Experiment 4, context freezing was strong in a group given footshock exposure but not in a group given eye shock US reexposure. There was no reinstatement observed in any experiment. With stimulus conditions that produce eyeblink conditioning and research designs that produce reinstatement in other forms of classical conditioning, we observed spontaneous recovery but not reinstatement of extinguished eyeblink CRs. This suggests that reinstatement, but not spontaneous recovery, is a preparation- or substrate-dependent phenomenon. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid Receptors Regulate the Extinction of Pavlovian Fear Conditioning.

Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of fear to an extinguished conditioned stimulus: Two roles for context.

The authors studied the role of context in reinstatement. Freezing was reinstated when the conditioned stimulus (CS) was extinguished in 1 context and rats moved to another context for reexposure to the shock unconditioned stimulus (US) and test. It was also reinstated (rather than renewed) when rats were shocked in the extinction context and moved to another context for test. This reinstatement was CS specific and reduced by nonreinforced exposures to the extinction context. Rats shocked in the context in which a stimulus had been preexposed froze when tested in another context. These findings suggest 2 roles for context in reinstatement: conditioning of the test context (M. E. Bouton, 1993) and mediated conditioning by the extinction context (P. C. Holland, 1990). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid reacquisition of fear to a completely extinguished context is replaced by transient impairment with additional extinction training.

A series of experiments studied reacquisition of fear reactions to a completely extinguished context. Reacquisition was rapid when reconditioning occurred as soon as the fear reactions were completely extinguished, showing that the original conditioning was intact. However, when reconditioning occurred after massive extinction training, fear reactions were depressed but then recovered across a long retention interval. This recovery was due to reconditioning and was similar to that produced by conditioning a massively preexposed context. These results show that massive extinction converts a potentially dangerous context into one that is merely familiar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental renewal in human participants.

Two experiments with human participants are presented that differentiate renewal from other behavioral effects that can produce a response after extinction. Participants played a video game and learned to suppress their behavior when sensor stimuli predicted an attack. Contexts (A, B, & C) were provided by fictitious galaxies where the game play took place. In Experiment 1, participants who received conditioning in A, extinction in B, and testing in A showed some context specificity of conditioning during extinction and a recovery of suppression on test. Experiment 2 demonstrated recovery of extinguished responding when participants were conditioned in A, extinguished in B, and tested in C, a third, neutral context. The experiment also demonstrated that the context of extinction did not control performance by becoming inhibitory. Results are discussed in terms of mechanisms that can produce a response recovery after extinction. The experiments demonstrated a renewal effect: a response recovery that was not attributable to the contexts acting as simple conditioned stimuli and is the first work with human participants to conclusively do so. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased spontaneous recovery with increases in conditioned stimulus alone exposures.

A series of experiments used the compound test procedure (Rescorla, 2002) to measure the size of spontaneous recovery of freezing responses by rats to a latently inhibited and/or extinguished conditioned stimulus (CS). The size of recovery was greater: to a pre-exposed and conditioned CS than to a CS just conditioned or just pre-exposed; to an extensively pre-exposed or extinguished CS than to a moderately pre-exposed or extinguished CS; and to a pre-exposed and extinguished CS than to a CS just pre-exposed or just extinguished. These results show that the size of recovery is proportional to the size of the depression produced by CS-alone exposures regardless of whether they occurred before, after, or both before and after conditioning. The results are discussed in terms of some contemporary models of recovery and of the inferences permitted by the use of the compound assessment technique. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Slow reacquisition following extinction: Context, encoding, and retrieval mechanisms.

Investigated the slow reacquisition (RAQ) of responding in rats that occurs when the conditioned stimulus/stimuli (CS) and unconditioned stimulus/stimuli (UCS) are paired again after prolonged extinction training. In Exp 1, an extinguished CS acquired less suppression than a novel CS during a final conditioning phase, but more suppression than CSs that had received comparable nonreinforcement without initial conditioning. In Exp 2, CS–UCS pairings resumed in the context of extinction caused the least RAQ of suppression: Pairings in a neutral context produced better RAQ, while return of the CS to the conditioning context caused an immediate renewal of responding to the CS. In Exp 3, a return of the CS to the extinction context after RAQ training caused renewed extinction performance and interfered with performance appropriate to RAQ. This effect was not due to demonstrable inhibitory conditioning of the extinction context. Results suggest that representations of conditioning and extinction (or CS–UCS and CS–no UCS relations) are both retained through extinction and that performance appropriate to either phase can be cued by the corresponding context. RAQ may thus be slow when the context retrieves an extinction memory. Similar mechanisms may also play a role in other Pavlovian interference paradigms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of context in re-acquisition of extinguished alcoholic beer-seeking.

We studied the role of context in reacquisition of extinguished reward-seeking. Rats were trained to respond for alcoholic beer, then extinguished and retrained. Reacquisition was faster than acquisition regardless of whether retraining occurred in the original training context, the extinction context, a novel context, or a context with a mixed history of reinforcement. Reacquisition was also rapid after extended extinction training. Nonetheless, context did significantly influence reacquisition via affecting latency to first response: rats took significantly longer to initiate responding when tested in the extinction context. These results suggest that reacquisition of drug and reward seeking is determined by an inhibitory influence caused by the extinction context and a facilitatory influence caused by reintroduction of the reinforcer (Bouton, 1993). (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Differential effects of training intertrial interval on acquisition of trace and long-delay fear conditioning in rats.

Many factors govern conditioning effectiveness, including the intertrial interval (ITI) used during training. The present study systematically varied the training ITI during both trace and long-delay fear conditioning. Rats were trained using one of six different ITIs and subsequently tested for conditioning to the white noise conditioned stimulus (CS) and the training context. After trace conditioning, percent freezing to the CS was positively correlated with training ITI, whereas percent freezing to the context was negatively correlated with training ITI. In contrast, when rats were trained using a long-delay paradigm, freezing during the CS test session did not vary as a function of training ITI; rats exhibited robust freezing at all ITIs. The long-delay conditioned rats exhibited relatively low levels of freezing during the context test. Thus, trace is more sensitive than long-delay fear conditioning to variations in the training ITI. These data suggest that training ITI is an important variable to consider when evaluating age or treatment effects, where the optimal ITI may vary with advancing age or pharmacological treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time-specific extinction and recovery of the rabbit's (Oryctolagus cuniculus) conditioned nictitating membrane response using mixed interstimulus intervals.

Extinguishing a conditioned response (CR) has entailed separating the conditioned stimulus (CS) from the unconditioned stimulus (US). This research reveals that elimination of the rabbit nictitating membrane response occurred during continuous CS-US pairings. Initial training contained a mixture of 2 CS-US interstimulus intervals (ISIs), 150 ms and 500 ms. The CRs showed double peaks, one for each ISI. When the 150-ms ISI was removed, its CR peak showed 2 hallmarks of extinction: a decline across sessions and spontaneous recovery between sessions. When a further stage of training was introduced with a distinctive CS using the 150-ms ISI, occasional tests of the original, extinguished CS revealed another hallmark of extinction, specifically, strong recovery of the 150-ms peak. These results support both abstract and cerebellar models of conditioning that encode the CS into a cascade of microstimuli, while challenging theories of extinction that rely on changes in CS processing, US representations, and contextual control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dorsal hippocampus involvement in trace fear conditioning with long, but not short, trace intervals in mice.

Placing a "trace" interval between a warning signal and an aversive shock makes consolidation of the memory for trace conditioning hippocampus dependent. To determine the trace at which memory consolidation requires the hippocampus, mice were trained with 0-s, 1-s, 3-s, or 20-s trace intervals and tested for freezing to context and tone. Posttraining dorsal hippocampus (DH) lesions decreased context conditioning regardless of trace interval. However, DH lesions attenuated only the 20-s trace tone freezing. Like eyeblink conditioning, the DH is necessary for trace fear conditioning only at long trace intervals, but the time scale for the effective interval in fear conditioning is about 40 times longer. Manipulations that alter trace fear conditioning with short trace intervals probably do not reflect altered DH function. Given this difference in time scale along with the use of posttraining DH lesions, hippocampus dependency of trace conditioning is not related to a bridging function or response timing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)