The effect of D-cycloserine on immediate vs. delayed extinction of learned fear

We compared the effect of D-cycloserine (DCS) on immediate (10 min after conditioning) and delayed (24 h after conditioning) extinction of learned fear in rats. DCS facilitated both immediate and delayed extinction when the drug was administered after extinction training. However, DCS did not facilitate immediate extinction when administered prior to extinction training (i.e., when the interval between drug administration and shock was reduced). In addition, administering five, but not two, shocks prior to extinction training disrupted the facilitating effects of DCS on delayed extinction. These results suggest that aversive experiences prior to DCS administration can prevent it from facilitating extinction.     

普萘洛尔修复即刻消退产生的二次创伤

恐惧消退能力的受损是创伤后应激障碍(posttraumatic stress disorder, PTSD)的标志之一。以往的研究表明, 相较于延迟消退, 恐惧获得后短时间内进行的消退训练不能形成长时程的消退记忆, 这一现象被称为即刻消退缺损。然而, 目前并不清楚这种缺损是一次性的, 还是会继续影响其后的重消退。实验1中, 大鼠在恐惧习得后1小时(即刻消退)或24小时(延迟消退)开始进行消退训练, 24小时后进行重消退, 再24小时后进行消退记忆的测试。结果显示, 与延迟消退相比, 即刻消退效果缺损, 并引起第二天的重消退也出现效果缺损。实验2中, 恐惧获得后立即给予大鼠盐水或β-肾上腺素受体阻断剂普萘洛尔(10 mg/kg, i.p.), 然后测试即刻消退和重消退的效果。结果显示, 普萘洛尔虽没有阻止即刻消退的缺损, 但避免了重消退出现缺损。总之, 严重创伤后的即刻消退不但无法有效抑制恐惧反应, 还可能造成二次创伤, 会损害恐惧消退能力, 而普萘洛尔可修复即刻消退引起的重消退缺损。这些结果将有助于我们加深对PTSD病理机制和早期干预后果的认识。     

Retention interval and intertrial interval in a serial learning or delayed discrimination task

In each of four experiments, rats were provided with the same three-event decreasing series (18-1-0) of 0.045-g food pellets in a runway. Tracking, running fast to 18 pellets and running slow to 1 and 0 pellets, was investigated as a function of the temporal interval elapsing between the events of the series (the retention interval), shifts in retention interval, and number of trials each day (or the intertrial interval), a trial being defined as presentation of each of the three events of the series. Neither retention interval, which varied from 15 s to 30 min in various investigations, nor shifts in retention interval affected tracking when only one trial was given each day. But when more than one daily trial was given, tracking was acquired more slowly and was disrupted by a shift in retention interval from 15 s to 5 min. Tracking was also disrupted by a shift from one to two trials each day. These results indicate that when given one 18-1-0 trial each day, the rat partitions events on a first-event/subsequent-event basis; that little forgetting occurs even at long retention intervals; that somewhat different memories signal events when one or more than one 18-1-0 trial occurs each day; and that retention interval deficits can arise owing to the same or similar memories' signaling different events. The results described limit the generality of three hypotheses suggested in two recent investigations: that as retention interval increases, rats find it increasingly difficult to remember and utilize serial position cues; that tracking in serial tasks is not influenced by number of trials each day; and that there are specific stimuli associated with each retention interval which, when changed, necessarily disrupt performance.     

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.     

Response duration is sensitive to both immediate and delayed reinforcement

We investigated the duration of lever pressing by rats when the delivery of appetitive reinforcers was contingent upon response duration. In the first experiment, response durations increased when duration requirements were imposed, and they decreased when duration requirements were removed. This effect occurred whether reinforcers were immediate or delayed by 8 s. In order to maintain the integrity of the delay intervals, reinforcer delivery was dependent upon both lever depression and release. In a second experiment, lever depression only and a response duration of at least 4 s were required for reinforcer delivery. Compared to immediate reinforcement conditions, delayed reinforcers increased both variability and the length of the maximum response durations. In a third experiment, immediate reinforcers were delivered contingent upon lever depression and release under a variety of duration requirements. Median lever‐press durations tracked the contingencies rapidly. Across all three experiments, rats emitted numerous response durations that were too short to satisfy the reinforcer requirements, and bimodal distributions similar to those produced by differential reinforcement of low rate schedules were evident for most rats. In many aspects, response duration responds to reinforcement parameters in a fashion similar to rate of discrete responding, but an examination of this continuous dimension of behavior may provide additional information about environment–behavior relationships.     

Reliability estimates for the immediate and delayed memory tasks

The Immediate and Delayed Memory Tasks are variations of the Continuous Performance Test. While previous research with the tasks has focused on group performance across multiple blocks and sessions, reliability estimates have not been established. We estimated reliability (1) between blocks of a single testing session (N=106), (2) across four sessions within a single testing day (N=20), and (3) across sessions on four consecutive testing days (N=20). Analyses indicated that the primary variable of interest, i.e., commission of errors, showed acceptable reliability within and across testing periods.     

A fixed interval schedule in which the interval is initiated by a response

The fixed interval schedule described requires the animal to initiate every time interval by making a response on a bar other than the one on which it is reinforced. This response, R_A, demarcates the postreinforcement pause (S^R-R_A interval) from the fixed interval pause (R_A-R_B interval) so that these pauses may be measured separately. Twelve rats and three monkeys, working in two-bar Skinner boxes, were trained and stabilized on this schedule. The resulting performances, presented for individual animals, are analyzed in terms of (1) the relative frequencies with which the animal waits various lengths of time between consecutive responses, (2) the relative frequencies with which various rates of responding appear, (3) the change in response rate throughout the fixed interval, (4) the average length of the postreinforcement pause, (5) the relative frequencies with which the animal waits different lengths of time between the R_A and the first R_B, and (6) the average inter-response time as a function of the rank order in the fixed interval of the inter-response time. The joint interpretation of the several measures taken leads to the following conclusions: 1. The probability of an R_B increases throughout the fixed interval. 2. The increase is discontinuous at the first R_B, at which point the probability increases sharply. 3. The frequency distributions of R_A-R_B pauses exhibit three discrete types of behavior with no intermediate cases. 4. The (main) mode of R_A-R_B interval length usually occurs just below the fixed interval requirement.     

The exclusive induction of extinction is gated by BDNF

We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268 activity in this region. Here we show that by infusing a recombinant brain-derived neurotrophic factor (rBDNF) directly into the brain of rats, that high levels of mature BDNF in the hippocampus at retrieval constrain the extinction of the fear memory after prolonged memory recall. We also show after a short CS exposure that reconsolidation was impaired using antisense oligonucleotides targeting Zif268, and that, similarly, reductions in conditioned behavior were observed after prolonged CS presentation when extinction is constrained by high levels of BDNF. This is direct evidence that in the mammalian brain extinction proceeds exclusively after prolonged CS exposure. In addition, that BDNF activity in the hippocampus contributes to a molecular switch for the extinction of hippocampal-dependent memory.     

When immediate losses are followed by delayed gains: Additive hyperboloid discounting models

Psychonomic Bulletin & Review - Discounting research has tended to focus on one simple situation, choice between an immediate, smaller gain and a larger, delayed gain, that is assumed by many...     

Evidence for recovery of fear following immediate extinction in rats and humans

Fear responses can be eliminated through extinction, a procedure involving the presentation of fear-eliciting stimuli without aversive outcomes. Extinction is believed to be mediated by new inhibitory learning that acts to suppress fear expression without erasing the original memory trace. This hypothesis is supported mainly by behavioral data demonstrating that fear can recover following extinction. However, a recent report by Myers and coworkers suggests that extinction conducted immediately after fear learning may erase or prevent the consolidation of the fear memory trace. Since extinction is a major component of nearly all behavioral therapies for human fear disorders, this finding supports the notion that therapeutic intervention beginning very soon after a traumatic event will be more efficacious. Given the importance of this issue, and the controversy regarding immediate versus delayed therapeutic interventions, we examined two fear recovery phenomena in both rats and humans: spontaneous recovery (SR) and reinstatement. We found evidence for SR and reinstatement in both rats and humans even when extinction was conducted immediately after fear learning. Thus, our data do not support the hypothesis that immediate extinction erases the original memory trace, nor do they suggest that a close temporal proximity of therapeutic intervention to the traumatic event might be advantageous.     

Memorial consequences of multiple-choice testing on immediate and delayed tests

Multiple-choice testing has both positive and negative consequences for performance on later tests. Prior testing increases the number of questions answered correctly on a later test but also increases the likelihood that questions will be answered with lures from the previous multiple-choice test (Roediger & Marsh, 2005). Prior research has shown that the positive effects of testing persist over a delay, but no one has examined the durability of the negative effects of testing. To address this, subjects took multiple-choice and cued recall tests (on subsets of questions) both immediately and a week after studying. Although delay reduced both the positive and negative testing effects, both still occurred after 1 week, especially if the multiple-choice test had also been delayed. These results are consistent with the argument that recollection underlies both the positive and negative testing effects.