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)     

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)     

Recent Exposure to a Dangerous Context Impairs Extinction and Reinstates Lost Fear Reactions.

Rats were shocked in a context and then exposed to that context in the absence of shock. Shorter intervals between these extinction trials produced more long-term freezing than did longer ones, and shorter intervals between the final extinction trial and test produced more freezing than did longer ones. A short interval between a context extinction trial and test with an extinguished conditioned stimulus (CS) produced more freezing than did a longer one, and a short interval between a nonreinforced context exposure and an extinguished CS reinstated freezing when the CS was tested 24 hr later. The results suggest that recent fear acts to favor subsequent retrieval of the memory formed at conditioning rather than extinction and to render the retrieved memory more salient. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Facilitation of fear extinction by midbrain periaqueductal gray infusions of rb101(s), an inhibitor of enkephalin-degrading enzymes.

μ-Opioid receptors in the ventrolateral quadrant midbrain periaqueductal gray (vIPAG) contribute to extinction of conditioned fear. The present experiment studied whether fear extinction could be facilitated by infusions of a peptidase inhibitor that reduces catabolism of vIPAG enkephalins. Rats were trained to fear an auditory conditioned stimulus. Fear was then extinguished. Extinction training was preceded by infusions of vehicle or RB101(S), an inhibitor of enkephalin catabolising enzymes. RB101(S) dose dependently facilitated extinction as indexed by performance during extinction and on a drug-free test. This facilitation was not observed when RB101(S) was infused outside the vIPAG. These results confirm that vIPAG endogenous opioids contribute to fear extinction and show that extinction can be facilitated by manipulations that increase vIPAG opioid neuromodulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Six experiments studied the role of conditioned stimulus (CS) familiarity in determining the effects of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 on fear extinction. Systemic administration of MK-801 (0.1 mg/kg) impaired initial extinction but not reextinction learning. MK-801 impaired reextinction learning when the CS was relatively novel during reextinction training but not initial extinction learning when the CS was relatively familiar during initial extinction training. A context change failed to reinstate the sensitivity of initial fear extinction learning about a relatively familiar CS to MK-801. These experiments show that CS familiarity is an important determinant of effects of MK-801 on fear extinction learning: MK-801 impaired extinction learning about novel stimuli but spared extinction learning about familiar stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of context on performance to conditioned stimuli with mixed histories of reinforcement and nonreinforcement.

Five conditioned suppression experiments, with 160 Wistar rats, explored the role of the conditioning history of the conditioned stimulus (CS) in determining the effects of contextual fear on performance to the CS. Contextual fear was produced by postconditioning exposure to unconditioned stimulus/stimuli (UCS) alone in the context of conditioning; it was independently assessed with context-preference tests. When the number of reinforced and nonreinforced trials was equated across extinction, partial reinforcement, and latent inhibition procedures, only the extinction procedure produced a CS whose performance was subsequently affected (i.e., augmented) by contextual fear. Contextual fear's relatively unique augmenting effect on fear of an extinguished CS was abolished by extensive, but not by less extensive, reacquisition training. Results indicate that, depending on the CS's conditioning history, contextual fear either augments or has little effect on fear of the CS. It is suggested that augmentation by context should be viewed as the restoration of fear that is otherwise depressed by extinction. (28 ref) (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)     

The effects of neurotoxic hippocampal lesions on two effects of context after fear extinction.

Three conditioned suppression experiments with rats examined the role of the hippocampus in 2 effects of context after extinction. Reinstatement is the context-specific recovery of fear to an extinguished conditioned stimulus (CS) that occurs following independent presentations of the unconditioned stimulus (UCS), after extinction. Renewal is the recovery of fear when the CS is presented in the context in which it was conditioned, after extinction in a different context. Results indicated that neurotoxic lesions of the hippocampus, performed before conditioning, abolished reinstatement, which depends on context–UCS associations, but not renewal, which does not. This dissociation is not the result of differences in the recentness of context learning that ordinarily governs the 2 effects. The results suggest that the hippocampus is necessary for some, but not all, types of contextual learning. (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)     

Blocking, Unblocking, and Overexpectation of Fear: A Role for Opioid Receptors in the Regulation of Pavlovian Association Formation.

Injection of the opioid receptor antagonist naloxone facilitated acquisition of fear to contextual and auditory conditioned stimuli (CSs) in Experiments 1A and 1B. Experiment 2 showed that prior conditioning to a distinctive context blocked conditioning to an auditory CS. Blocking of CS fear was prevented by administrations of naloxone or increases in footshock intensity. Blocking of CS fear was facilitated by decreases in footshock intensity in a naloxone-reversible manner. Experiment 3 showed that compound conditioning of two CSs, each previously and separately paired with shock, produced overexpectation of fear that was reversed by naloxone. These results are consistent with a role for opioid receptors controlling Pavlovian association formation by regulating the discrepancy (A--ΣV) described by R. A. Rescorla and A. R. Wagner (1972). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genetic variation among Trypanosoma cruzi populations

Four experiments examined the effect of naloxone pretreatment on the expression and extinction of ethanol-induced conditioned place preference (experiments 1, 2, 4) or conditioned place aversion (experiments 1, 3). DBA/2 J mice received four pairings of a distinctive tactile (floor) stimulus (CS) with injection of ethanol (2 g/kg) given either immediately before or after 5-min exposure to the CS. A different stimulus was paired with injection of saline. Pre-CS injection of ethanol produced conditioned place preference, whereas post-CS injection of ethanol produced conditioned place aversion. Both behaviors extinguished partially during repeated choice testing after vehicle injection. Naloxone (10 mg/kg) had little effect on the initial expression of conditioned place preference, but facilitated its extinction. Moreover, repeated naloxone testing resulted in the expression of a weak conditioned place aversion to the CS that initially elicited a place preference. In contrast, naloxone (1.5 or 10 mg/kg) enhanced expression of conditioned place aversion, thereby increasing its resistance to extinction. A control experiment (experiment 4) indicated that repeated testing with a different aversive drug, lithium chloride, did not affect rate of extinction or produce an aversion to the CS previously paired with ethanol. These findings do not support the suggestion that naloxone facilitates the general processes that underlie extinction of associative learning. Also, these data are not readily explained by the conditioning of place aversion at the time of testing. Rather, naloxone's effects appear to reflect a selective influence on maintenance of ethanol's conditioned rewarding effect, an effect that may be mediated by release of endogenous opioids. Overall, these findings encourage further consideration of the use of opiate antagonists in the treatment of alcoholism.     

Central CRF receptor antagonist α-helical CRF9-41 blocks reinstatement of extinguished fear: The role of the bed nucleus of the stria terminalis.

The present experiments assessed the necessity of central CRF in reinstatement of extinguished fear. Using the fear-potentiated startle procedure, rats were given light-shock pairings (fear conditioning) followed by light-alone extinction training. Rats were then given unsignaled shocks to reinstate fear to the light conditioned stimulus (CS). Intracerebroventricular administration of the CRF antagonist α-Helical CRF9-41 prior to reinstatement training dose-dependently prevented reinstatement. Further, α-Helical CRF9-41 administration prior to reinstatement training or the test for reinstatement of fear to the extinguished CS prevented reinstatement at both treatment times, suggesting that CRF activity is critical for this type of return of fear to an extinguished CS. The abolition of reinstatement by drug administration was not due to state-dependent learning, as rats treated with the drug prior to both reinstatement training or testing also failed α-Helical CRF9-41 in the bed nucleus of the stria terminalis suggested that this area is a site at which central CRF is involved in this form of relapse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine enhances the expression of fear-potentiated startle: Evaluation of state-dependent extinction and the shock-sensitization of acoustic startle.

Cocaine's effects on fear extinction and on the shock-sensitization of acoustic startle were examined. Following fear acquisition, rats exposed to the nonreinforced CS after cocaine administration demonstrated significant levels of fear-potentiated startle when evaluated in the drug-free state. The CS also increased startle amplitudes in subjects extinguished and tested with cocaine, indicating that mechanisms other than state-dependent learning are involved in the extinction deficit. The presentation of 10 footshocks augmented acoustic startle, and the shock enhancement was unaffected by cocaine preexposure. These data indicate that the aversive consequences of footshock relevant to the acquisition of conditional fear are not sensitized by the drug. It was suggested that cocaine reinforces fear responding to a threatening stimulus. (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)     

Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning.

Trace fear conditioning is a learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single neuron activity was recorded from the prelimbic and infralimbic areas of the medial prefrontal cortex in rats during trace fear conditioning or nonassociative unpaired training. Prelimbic neurons showed learning-related increases in activity to the CS and US, whereas infralimbic neurons showed learning-related decreases in activity to these stimuli. A subset of prelimbic neurons exhibited sustained increases in activity during the trace interval. These sustained prelimbic responses may provide a bridging code that allows for overlapping representations of CS and US information within the trace fear conditioning circuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential control by context in the inflation and reinstatement paradigms.

Examined, in 5 conditioned suppression experiments, the influence of summation between fear of the CS and the context in experimental paradigms in which the rat is exposed to UCSs following conditioning or extinction. Context-preference tests assessed contextual fear. In Exps I–III with 88 female Wistar rats, the inflation paradigm, in which fear of a CS paired with a weak UCS is enhanced by exposure to intense UCS alone, was investigated. Results show that the contextual fear that was present when the target CS was tested was reduced by presenting the intense UCSs in a different context, by exposing Ss to the context following their presentation, and by signaling the intense UCSs with a 2nd CS. In Exp IV with 32 female Wistar rats, UCS exposures following conditioning or extinction both produced contextual fear, but only fear of the extinguished CS was reinstated by that fear. In Exp V with 32 female Wistar rats, identical amounts of contextual fear reinstated fear of an extinguished CS, but not a nonextinguished CS, when the 2 types of CSs were arranged to evoke comparable amounts of fear prior to testing. It is suggested that contextual fear plays a role in the reinstatement paradigm but not in the inflation paradigm. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual control of the extinction of conditioned fear: Tests for the associative value of the context.

When male Wistar rats received pairings of a CS with shock in one context and then extinction of the CS in another, fear of the CS was renewed when the CS was returned to and tested in the original context (Exps I and III; 40 Ss). No such renewal was obtained when the CS was tested in a 2nd context after extinction had occurred in the conditioning context (Exp IV; 24 Ss). In Exp II, shocks presented following extinction reinstated fear of the CS, but only if they were presented in the context in which the CS was tested. In each experiment, the associative properties of the contexts were independently assessed. Contextual excitation was assessed primarily with context-preference tests in which Ss chose to sit in either the target context or an adjoining side compartment. Contextual inhibition was assessed with summation tests. Although reinstatement was correlated with demonstrable contextual excitation present during testing, the renewal effect was not. There was no evidence that contextual inhibition developed during extinction. Results suggest that fear of an extinguished CS can be affected by the excitatory strength of the context but that independently demonstrable contextual excitation or inhibition is not necessary for contexts to control that fear. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporally massed CS presentations generate more fear extinction than spaced presentations.

Rodent fear conditioning models both excitatory learning and the pathogenesis of human anxiety, whereas extinction of conditional fear is a paradigm of inhibitory learning and the explicit model for behavior therapy. Many studies support a general learning rule for acquisition: Temporally spaced training is more effective than massed training. The authors asked whether this rule applies to extinction of conditional fear in mice. The authors find that both short- and long-term fear extinction are greater with temporally massed presentations of the conditional stimulus (CS). The data also indicate that once CS presentations are sufficiently massed to initiate, or "induce," extinction learning, further CS presentations are more effective when spaced. (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)