Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli.

The GABAa agonist, muscimol (0.5 μg in 0.5 μl saline), or vehicle was infused into the lateral and basal amygdala nuclei prior to fear conditioning or testing in rats. Rats given muscimol before conditioning and saline before testing showed much less freezing to the conditioned stimulus (CS) and the context than did controls given saline before training and testing. Rats given saline before training and muscimol prior to testing also showed low levels of freezing to the CS and the context. In follow-up procedures, rats with acquisition initially blocked by pretraining muscimol infusions froze in a manner similar to that of controls when retrained and retested with saline infusions. Rats trained with saline but tested with muscimol presumably became conditioned but could express the learning. When retested with saline, they froze in the same manner as controls. Thus, activity in the lateral and basal amygdala appears to play an essential role in the acquisition and expression of fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disruptive effects of posttraining perirhinal cortex lesions on conditioned fear: Contributions of contextual cues.

Lesions placed in the rostral perirhinal cortex (rPRh) after fear conditioning interfere with the expression of conditioned fear responses elicited by auditory and visual conditioned stimuli when these stimuli are presented in a context that differs from the conditioning context. The present study examined whether lesions of the rPRh have similar effects when animals are tested in the conditioning context. Two days after male rats received classical fear conditioning, involving the pairing of an auditory CS with footshock, bilateral electrolytic lesions were produced in the rPRh. Five days later conditioned freezing behavior was measured during a 60-s exposure to the CS in a novel context and then 1 hr later in the conditioning context. There were 3 major findings: rPRh-lesioned Ss froze significantly less than controls to the CS in the novel context, thus confirming previously reported findings. rPRh-lesioned Ss also froze less than controls to the CS in the conditioning context, but froze significantly more to the CS in the conditioning than in the novel context, suggesting that at least part of the deficit in the novel context is due to the absence of contextual cues. Ss with rPRh lesions froze significantly less than controls to the conditioning context itself.… (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)     

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS–unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning. (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)     

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.     

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)     

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)     

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)–unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS–US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and were trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal lesions alter conditioning to conditional and contextual stimuli

The control of conditioned fear behaviour by a conditional stimulus (CS) and contextual stimuli (CXT) was compared in rats with lesions to the hippocampus (HPC) or neocortex (CO), and operated controls (OC). After classical fear conditioning in a distinctive context, rats were subsequently tested in the presence of the CS and CXT (CS + CXT), the CS alone (CS-only), or context alone (CXT-only). Two experiments were conducted in which conditioned fear was measured by an active avoidance response (experiment 1) or by response suppression (experiment 2). Groups did not differ in acquiring the conditioned fear response, as measured in the CS + CON test but, in both experiments, hippocampal (HPC) groups exhibited more conditioned fear behaviour than controls in the CXT-Only and CS-Only conditions. It was suggested that control rats conditioned the fear response to a stimulus complex that incorporated the CS and CTX. Rats with HPC lesions did not form this association between the stimulus elements; instead they segregated the CS and CXT and formed independent associations between the conditioned response (CR) and each component. In showing that HPC damage disrupts the process of forming associations between environmental stimuli and that the effect is not restricted to contextual cues, the results help to resolve apparently contradictory findings regarding the role of HPC in contextual information processing.     

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)     

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)     

Anterograde amnesia for Pavlovian fear conditioning and the role of one trial overshadowing: Effects of preconditioning exposures to morphine in rat.

Four experiments studied anterograde deficits in Pavlovian fear conditioning following prolonged exposure to the μ-opioid receptor agonist morphine. Injections of morphine produced temporally graded anterograde amnesia characterized by deficits in contextual and conditioned-stimulus (CS) conditioning 1 or 7 days and selective impairment in CS conditioning 21 days after last injection. This anterograde deficit in conditioning did not recover across a retention interval, was absent when rats were tested immediately after conditioning, and required the presence of an auditory CS. These results suggest that anterograde deficits in Pavlovian fear conditioning emerged from differences in susceptibility to 1-trial overshadowing of context by CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of GABA and anxiety in the reconsolidation of conditioned fear.

The current study examined the effects of systemic administration of a GABA agonist [midazolam (MDZ)] and a GABA antagonist (bicuculline) on fear responding after brief CS exposure, a procedure thought to involve memory reconsolidation. Using a contextual fear-conditioning paradigm, rats were initially given two context-shock training trials, followed 24 hrs later by a 90-s context exposure (reactivation), and 24 hrs later by a 3-min context test. In Experiment 1, MDZ (2 mg/kg, i.p.), whereas in Experiment 2, bicuculline (1 mg/kg, i.p.), was administered immediately after reactivation. MDZ reduced conditioned freezing, whereas bicuculline only marginally potentiated conditioned freezing. The MDZ fear disruption effect did not occur in the absence of reactivation, and was evident 10 days after the initial test. Experiment 3 induced high levels of baseline anxiety using the single prolonged stress paradigm, and replicated the essential procedure of Experiment 1. Results indicated that MDZ fear disruption did not differ between high and low anxiety rats. The data suggest the involvement of GABA receptors in reconsolidation processes, and the possible clinical use of MDZ in fear reduction with brief reexposure. (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)     

Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.

This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. (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)     

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

Reports an error in the original article by R. J. Frohardt et al (Behavioral Neuroscience, 2000 [Apr], Vol 114[2], 227-240). On page 229, there is an error in the Method section. The second full sentence on that page should read: Neurotoxic lesions of hippocampus were produced by injections of a mixture of 5.0 μg ibotenic acid and 5.0 μg NMDA per 0.5 ml of normal saline. (The following abstract of this article originally appeared in record 2000-15286-001): 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 two effects… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioid receptors regulate retrieval of infant fear memories: Effects of naloxone on infantile amnesia.

The authors examined the role of the endogenous opioid system in infantile amnesia for contextual fear conditioning. Rats that were 18 days of age received an aversive footshock in a novel context. Rats displayed conditioned fear when tested 1 min after training but not 24 hr after training. Systemic injection of the opioid receptor antagonist naloxone prior to test, but not immediately after training, alleviated infantile amnesia. Naloxone also alleviated infantile amnesia when injected prior to test 7 days after training. These effects of naloxone were due to actions on central rather than peripheral opioid receptors and were not due to any tendency of the drug to produce fear or freezing. These results show that central opioid receptors regulate retrieval of fear memories in infant rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of forward or simultaneous conditioned stimulus-unconditioned stimulus intervals on the defensive behavior system of the Norway rat (Rattus norvegicus).

To test several predictions derived from a behavior-systems approach, the authors assessed Pavlovian fear conditioning in rats after 30 trials of forward, simultaneous, or unpaired training. Direct evidence of conditioned fear was collected through observation of flight and freezing reactions during presentations of the conditioned stimulus (CS) alone. The authors also tested the CS's potential to reinforce an instrumental escape response in an escape-from-fear paradigm. On the one hand, rats that received forward training showed conditioned freezing, but no conditioned flight was observed. On the other hand, rats that received simultaneous training showed conditioned flight, but no conditioned freezing was observed. Rats that received either forward or simultaneous pairings showed instrumental learning of the escape-from-fear response. Implications for several theories of Pavlovian conditioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)