Stress-enhanced fear learning in rats is resistant to the effects of immediate massed extinction

Enhanced fear learning occurs subsequent to traumatic or stressful events and is a persistent challenge to the treatment of post-traumatic stress disorder (PTSD). Facilitation of learning produced by prior stress can elicit an exaggerated fear response to a minimally aversive event or stimulus. Stress-enhanced fear learning (SEFL) is a rat model of PTSD; rats previously exposed to the SEFL 15 electrical shocks procedure exhibit several behavioral responses similar to those seen in patients with PTSD. However, past reports found that SEFL is not mitigated by extinction (a model of exposure therapy) when the spaced extinction began 24?h after stress. Recent studies found that extinction from 10?min to 1?h subsequent to fear conditioning "erased" learning, whereas later extinction, occurring from 24 to 72?h after conditioning did not. Other studies indicate that massed extinction is more effective than spaced procedures. Therefore, we examined the time-dependent nature of extinction on the stress-induced enhancement of fear learning using a massed trial's procedure. Experimental rats received 15 foot shocks and were given either no extinction or massed extinction 10?min or 72?h later. Our present data indicate that SEFL, following traumatic stress, is resistant to immediate massed extinction. Experimental rats showed exaggerated new fear learning regardless of when extinction training occurred. Thus, post-traumatic reactivity such as SEFL does not seem responsive to extinction treatments.     

Dissociative effects of different types and amounts of nonreinforced CS exposure on avoidance extinction and the CER

Two experiments examined the effectiveness of two amounts of flooding or response-prevention on hastening avoidance response extinction and on reducing CS-produced suppression of bar-pressing for food. In Experiment 1, 20 and 30 flooding trials were both shown to be effective in hastening the extinction of a well-learned shuttlebox avoidance response. In Experiment 2, rats trained under comparable conditions to those in Experiment 1 were tested following flooding for the CER in a different apparatus. The results indicated that 30, but not 20, flooding trials were sufficient to reduce the CER. In each experiment the results of additional control groups equated with the flooded groups for nonreinforced CS exposure also revealed a dissociation between the effectiveness of this CS time control procedure in hastening avoidance response extinction and in reducing the CER. Further comparisons showed that although 30 flooding trials did reduce the CER, the same total duration of nonreinforced CS Exposure in the form of avoidance extinction trials did not. Thus the context in which CS exposure occurs may affect the dynamics of extinction of the CER. The experiments are discussed in the broader context of dissociation of various indices of fear in humans.     

A rapid and sensitive method for measuring the conditional emotional response II: On-the-baseline excitatory conditioning and extinction

The present study outlines a rapid and sensitive on-the-baseline conditional emotional response (CER) procedure. Using rats as the experimental subject, the method detects delay conditioning, incubation, extinction and spontaneous recovery. In addition, the method detects conditional responding using electric shock ranging from 0.23 to 0.50 mA as the unconditional stimulus. Because of its speed and sensitivity, the method shelters the subject from unnecessary long-term deprivation and pain.     

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.     

Reevaluation of things past

The ability of rats to reevaluate previously presented information in light of subsequently provided information was evaluated using a CER (conditioned emotional response) procedure. In Experiment 1, rats suppressed responding to a compound light + tone stimulus that was repeatedly paired with shock. Groups of rats were then presented with only one element of the compound (the tone), either presented alone or paired with shock, for 15 days. During this 15-day period, two control groups received trials with the shock alone or neither stimulus nor shock. All of the rats were then tested with the other element of the compound (the light). Rats that had received the tone paired with shock during the intervening training continued to suppress to the light, whereas rats that had received the tone alone showed rapid extinction of the CER to light. The control groups showed that this effect was not due to the number of shock presentations received. A subsequent experiment also demonstrated that these results were not due to nonspecific stimulus effects. Apparently, a subsequent change in the associative strength of one element results in a similar change to the other element of a previously established compound stimulus.     

Dissociation between conditioned emotional response and extended avoidance performance

The present experiments examined the dissociation between the strength of a shuttlebox avoidance response (AR) and one index of fear of the avoidance CS. Avoidance response strength was indexed by resistance to extinction of the AR and by changes in response latency, and fear of the CS was indexed by the conditioned emotional response (CER) technique. Experiments 1, 2A, and 3A all found that rats trained to a criterion of 27 consecutive avoidance responses (CARs) showed response strength comparable or superior to rats trained to a criterion of 9 CARs. Experiments 2B and 3A demonstrated that rats trained to 27 CARs showed less suppression of bar pressing during the avoidance CS (less CER) than rats trained to 9 CARs. Experiment 3A also found that, when extinguished in the shuttlebox to a moderate criterion (5 consecutive trials without a response) before CER testing, rats trained to 9 CARs showed some, although not complete, loss of CER, whereas rats trained to 27 CARs showed no loss of CER. In Experiment 3B rats that took 1 vs 2 days to reach a criterion of 27 CARs were compared for their AR strength and for their CER. Although rats taking 2 days to reach criterion showed somewhat greater resistance to extinction of the AR than rats reaching criterion in 1 day, this variable had no apparent effect on the CER. Implications of the present results for current theories of avoidance learning are discussed.     

Variations in the sensitivity of instrumental responding to reinforcer devaluation

In five experiments hungry rats were trained to make a lever press response for a sucrose reinforcer. That sucrose was subsequently devalued by conditioning a food-aversion to it, and the ability of the rats to integrate knowledge about the instrumental contingency with that gained from aversion training was assessed in an extinction test. Experiment I showed successful integration following limited but not extended instrumental training. Experiment II suggested that the crucial factor was the spacing of training; successful integration was seen after massed but not distributed training. The third experiment implicated distributed experience with the reinforcer, rather than distributed response practice, in failures of integration. Experiment IV showed that if the distribution of food-aversion learning was dissimilar to that of instrumental training then a failure of integration could result; this finding was able to account for the distribution of training effects seen in previous studies, but not the effect of extended training. Experiment V replicated the extended training effect seen in Experiment I, and provided evidence that this may reflect the degree of exposure to the reinforcer rather than the extent of response practice.     

Factors influencing inhibitory stimulus control: discrimination training and prior non-differential reinforcement

In Exp. I, shallow U-shaped gradients of inhibition in the line-orientation dimension were obtained from birds that had a vertical (0°) line on a green surround correlated with extinction and a blank green surround correlated with reinforcement. Birds that had massed extinction in the presence of the 0° line showed flat gradients. Thus, discrimination training, but not massed extinction, appears to generate inhibitory control. In Exp. II, as in studies of control by a stimulus correlated with punishment, non-differential training across the line-orientation dimension preceded further sessions. Steep inverted gradients about the 0° line were obtained after discrimination training with the 0° line correlated with extinction. Gradients obtained after massed extinction tended to be flat. Again, discrimination training was critical in obtaining negative gradients of stimulus control.     

Retention of massed vs distributed response-prevention treatments in rats and a revised training procedure.

Two experiments were conducted to estimate the retention of response-prevention effects using massed vs distributed treatments in a model of animal avoidance-learning. In Exp. I, 120 rats were trained to avoid shock in a one-way platform avoidance apparatus. Groups received response-prevention treatment or nontreatment in a 36-min. massed session or in several sessions distributed over a four-day period. In Exp. II, 160 rats were given two trials of escape training in a one-way shuttle box. Groups received response-prevention treatment or nontreatment in a 24-min. session of massed or distributed treatments delivered in one day. Subjects in both studies were tested using a passive-avoidance paradigm immediately following treatment, 24 hours later, and 30 days later. Analysis showed that response-prevention treatments were effective in reducing avoidance behavior and there were no significant differences in retention of avoidance associated with massed vs distributed response-prevention treatments. Implications for animals and humans are discussed, and researchers are encouraged to change from a criterion training procedure to an escape procedure since the latter is a closer analogue to the human condition.     

Extinction of a running response as a function of reinforcement magnitude

Four groups of rats were trained on different sucrose solutions in a straight runway. Terminal running speed was a monotonic function of reinforcement magnitude. After training each group was subdivided, one subgroup being extinguished under spaced, the other under massed conditions. In spaced extinction the animals trained on non extreme reward magnitudes showed most resistance to extinction. It was concluded that resistance to extinction is an inverted U-shaped function of reinforcement magnitude found in training. The massed extinction trials were conducted with a very short inter-trial interval. The animals showed an immediate drop in running speed followed by a gradual recovery and a subsequent decline. The number of trials taken to reach the peak recovery speed was a function of reinforcement magnitude found in training. Results on both massed and spaced extinction trials were interpreted in terms of the facilitatory and inhibitory effects of momentary and conditioned frustration.     

Adrenergic transmission facilitates extinction of conditional fear in mice

Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS exposures trigger two opposing processes: (1) fear extinction, which is favored by CS massing, and (2) fear incubation (increase), which is favored by spacing. We here report the effects of manipulating the adrenergic system during massed or spaced CS presentations in fear-conditioned mice. We administered yohimbine (5 mg/kg), an alpha(2)-receptor antagonist, or propranolol (10 mg/kg), a beta-receptor antagonist, systemically prior to CS presentation sessions and recorded both short- and long-term changes in conditional freezing. Yohimbine treatment facilitated extinction of both cue and context fear with massed protocols. When given before spaced CS presentations, propranolol led to a persistent incubation of cue fear, whereas yohimbine led to persistent extinction, compared with vehicle-treated animals, which showed no change in fear. These results suggest that norepinephrine positively modulates the formation of fear extinction memories in mice. They also provide clear evidence that spaced CS presentations trigger both fear-reducing (extinction) and fear-increasing (incubation) mechanisms.     

Transfer of conditioned appetitive stimuli to conditioned aversive excitatory and inhibitory stimuli

The transfer of Pavlovian appetitive stimuli to Pavlovian aversive stimuli was examined in three experiments. In Experiment 1, rats received appetitive (Ap) conditioning designed to establish a flashing-light stimulus as either a CS+, CSo, or CS? for food, or to maintain it as a novel stimulus for US-alone subjects. Then, the stimulus was employed as a signal for weak shock in conditioned-emotional-response (CER) training. Both acquisition and extinction results showed that the ApCS+ facilitated and the ApCS? retarded aversive excitatory conditioning relative to the ApCSo and US-alone controls. Experiment 2 replicated the findings of Experiment 1 with both a moderate and a severe shock in CER training. In Experiment 3, different groups received the same appetitive conditioning as before, but to a flashing-light stimulus which was then employed as a signal for no shock in CER training. The ApCS? facilitated and the ApCS+ retarded aversive inhibitory conditioning relative to ApCSo and US-alone controls. Collectively, these findings establish that, in Pavlovian conditioning, transfer of an appetitive CS to an aversive excitor or inhibitor is facilitated by maintaining the initial conditioning contingency.     

Mechanisms of blocking by contextual stimuli

The influence of contextual stimuli on the conditioning and performance of responding to a discrete stimulus was examined in the US preexposure paradigm using both context shift manipulations and a measure of context conditioning. Four groups of rats received both repeated exposure to an electric shock US in one context (Context 1), and repeated nonshocked exposure to a second context (Context 2). Two additional groups of rats received exposure to these contexts, but never received shock presentations. Rats exposed to shock learned to escape from the stimuli of Context 1, but did not escape from the stimuli provided by Context 2. Rats not exposed to shock failed to escape from either context. All rats then received a single CER conditioning session in which four pairings of a 3-min noise CS and shock US were presented. Half the rats received those CS-US pairings in the excitatory Context 1, while the remaining rats received those pairings in the neutral Context 2. Finally, half the rats in each of the CER conditioning treatments received extinction test trials of the noise CS in Context 1, while the remaining rats received those test trials in Context 2. Thus, this design factorially manipulated the presence of excitatory or neutral contextual stimuli during both conditioning and testing of a discrete CS. In comparison with the two groups of rats never preexposed to shock alone, attenuation in acquisition of conditioned suppression observed during test trials occurred only when CER conditioning had been administered in the excitatory Context 1, and this effect was manifested when testing occurred in either the excitatory Context 1 or the neutral Context 2. These results support the model of R. A. Rescorla and A. R. Wagner (1972) (in A. H. Black & W. F. Prokasy (Eds.) Classical Conditioning II, pp. 64–99, New York: Appleton-Century-Crofts) which asserts that contextual stimuli and sicrete CSs compete for limited associative strength supportable by a given US.     

Aversive CSs suppress lever pressing for food but not the eating of free food

Forty rats received CER acquisition, half “on the baseline” (response lever present), half “off the baseline.” During initial CER extinction, Ss received: (a) normal CER extinction (lever available), (b) free food during CSs only (no lever), (c) free food during non-CSs only (no lever), or (d) free food during both CS and non-CS periods (no lever). While normal extinction Ss were highly suppressed in the presence of the CS, all free food groups readily ate but did not differ in eating latencies. On subsequent CER extinction trials on the baseline, those Ss which received free food during the CSs were no less suppressed than other Ss. These data offer no support for Estes' (1969) reciprocal inhibition explanation of CER and punishment, nor do they support a fear interpretation of CER.     

Reward schedule effects in extinction: Intertrial interval, memory, and memory retrieval

Rats were trained in a runway such that partial reward occurred on Trial 1 of the day and consistent reward on subsequent massed trials (Group PRT1), or consistent reward occurred on Trial 1 of the day and partial reward on subsequent massed trials (Group PRTM). Under spaced (24-hr) extinction, Group PRT1 was more resistant to extinction than Group PRTM and under massed (1-min) extinction, Group PRTM was more resistant to extinction than Group PRT1. These findings suggest that (a) distinctive stimuli are associated with Trial 1 of the day and with subsequent massed trials, (b) these distinctive stimuli function as retrieval cues for memories, memory retrieval being independent of intertrial interval, and (c) behavior in extinction is controlled by a stimulus compound consisting of the memory of nonreward plus stimuli which accompany the memory of nonreward on rewarded acquisition trials.     

Long-lasting and context-specific freezing preference is acquired after spaced repeated presentations of a danger stimulus in the crab Chasmagnathus

A visual danger stimulus elicits an escape response in the crab Chasmagnathus that declines after repeated presentations. Previous results report that such waning may be retained as context-signal memory (CSM) or signal memory (SM): CSM is long lasting, associative, and produced by spaced training, while SM is an intermediate memory, nonassociative, and produced by massed training. The performances of both spaced and massed trained crabs are here examined, using video analysis to determine topographic changes in the behavioral response during and after training. During spaced training, escape vanishes and is mainly replaced by freezing, while during massed training, escape decreases over trials without being replaced by any defensive response. After 24 h, the marked proclivity to freezing persists in spaced trained crabs, while a high level of escaping is shown by massed trained crabs. The long-lasting freezing preference of spaced trained crabs proves to be context-specific and apparent from the very first presentation of the danger stimulus at testing, though freezing is not triggered by the sole exposure to the context. We conclude (a) that freezing preference is the acquired response of the CSM process; (b) that CSM can be properly categorized as an instance of contextual conditioning and SM of classical habituation; (c) that CSM and SM are not two phases of a memory processing but two distinctly types of memory; and (d) that therefore, the temporal distribution of training trials has a drastic effect on crab's memory, more dramatic than that previously described. The possibility that massed and spaced presentations of the same stimulus may represent two different stimulus types is discussed.     

Extinction of the context and latent inhibition

The hypothesis that latent inhibition could be reduced by extinguishing the experimental context, that is, exposing the rats to the context between exposure to the conditional stimulus (CS) and conditioning, was tested. All experiments used the conditioned emotional response procedure. In Experiment 1, extinction was not effective when the animals were exposed to the clicker 40 times off the baseline of responding for food and when the clicker CS was partially reinforced with shocks during the test phase. In Experiments 2 and 3, latent inhibition could be reduced by extinction if the animals were exposed to the CS 24 or 16 times on-baseline, and if continuous reinforcement was used during the test. In Experiments 4, 5, and 6, we attempted to determine which variable was responsible for the discrepant results. In Experiment 4, extinction was effective with 20 or 40 on-baseline exposures to the CS, using continuous reinforcement during the test. In Experiment 5, extinction was not effective with exposure on- or off-baseline, using 24 exposures and partial reinforcement. Finally, in Experiment 6, extinction reduced latent inhibition using continuous, but not partial, reinforcement with 40 exposures off-baseline. From these results, we concluded that Wagner's model of habituation was not sufficient to account for latent inhibition and that a hybrid model, using both associative and cognitive representational processes, was necessary.     

Discriminative effects of massed extincttion

Prior studies have reported that generalization gradients are not steepened if periods of non-reinforcement in S− follow and are not interspersed with periods of reinforcement in S+. Sharper gradients are produced by this massed-extinction procedure if it is preceded by prior discriminative training on a dimension orthogonal to the S+, S− dimension. The present study, using pigeons, found that generalization gradients along the wavelength dimension were steepened by massed-extinction sessions in 570 nm that had been preceded by: (1) discriminative training in which the S+ was a 550-nm light and the S− was a black vertical line superimposed on the 550-nm light; (2) non-differential reinforcement training with a 550-nm light and a black vertical line superimposed on the 550-nm light; (3) reinforcement training with only the 550-nm light. Massed-extinction sessions were administered until the response rate in the presence of the 570-nm stimulus was one-tenth of the mean response rate in the presence of the 550-nm stimulus during prior reinforcement training. Prior studies have used a time-dependent criterion, rather than a response-rate criterion of extinction, and this difference may be responsible for the differences in the effects of massed extinction on stimulus control.     

Differential effects of progesterone and medroxyprogesterone on delay eyeblink conditioning in ovariectomized rats

Ovarian hormones modulate acquisition processes involved in classical conditioning. Although progesterone has been indirectly implicated, its role in classical conditioning of the eyeblink response has not been directly investigated. We assessed the effects of daily dosing of progesterone or medroxyprogesterone (MPA), a non-metabolized synthetic progestin, upon the acquisition of a classically conditioned eyeblink response in ovariectomized (OVX) female rats. Rats were dosed 4h prior to each training session with 0.1 or 1.5 mg/kg of either of these hormones or sesame oil. A delay conditioning paradigm was employed using a 500 ms conditioned stimulus coterminating with a 10 ms 10 V unconditioned stimulus. At the low dose, progesterone and MPA rats did differ from each other, with MPA-treated rats learning slower, but neither group differed from OVX-oil or Sham-oil controls. No group differences in acquisition were observed at the higher dose. During extinction trials, high-dose MPA-treatment and OVX-oil groups extinguished quicker than the high-dose progesterone-treated group. In addition, unconditional response (UR) amplitudes were lower in all OVX groups, regardless of hormone or oil treatment, compared to the sham-oil group. Since MPA did not affect extinction, it is likely the slower extinction in the progesterone-treated rats is due to a metabolite of progesterone. Corticosterone is discussed as a likely candidate for such a role. In addition, we found chronic absence of ovarian hormones decreased UR amplitudes, although differences in UR amplitudes were not associated with changes in the acquisition process. These results are discussed with respect to differences in the hormonal effects upon acquisition versus extinction processes and how these data may explain reports of learning differences in women based on oral contraceptive usage.     

On the minimal conditions for the development of a peak-shift and inhibitory stimulus control

Failures to obtain a peak-shift and inhibitory stimulus control following massed extinction in the presence of intra- and interdimensional stimuli confirm earlier results reported by Honig, Thomas, and Guttman (1959) and by Weisman and Palmer (1969). Peak-shifts and inhibitory stimulus control were observed when any of the following procedures intervened for 3 min between massed extinction and generalization testing: (1) S+ presented, responding reinforced; (2) S+ presented, responding not reinforced; or, (3) noncontingent food presented in the presence of a dark key. Behavioral contrast was shown not to be a necessary antecedent for the occurrence of peak-shift or inhibitory stimulus control.