The Reinforcing Effect of a Differentiating Stimulus

Twenty Sprague Dawley rats, aged 22 to 26 months were given subcutaneous injections of 4.5 mg/kg methylphenidate or distilled water. Twelve minutes after the single injection was given, rats began 90 trials of avoidance conditioning. Drug animals made significantly more correct responses than did the control animals. Results indicate that use of methylphenidate in aged rats improved avoidance learning.     

Acquisition and extinction of signaled avoidance as a function of intermittent reinforcement

Signaled, shuttle-box avoidance responding in female rats of the Fischer₃₄₄ strain was examined as a function of four separate contingencies of intermittent reinforcement. In Experiment 1, when avoidance responses during acquisition were reinforced 25% of the time with prompt CS termination, animals responded equally often during acquisition and significantly more often during extinction than animals who received such reinforcement on a 100% schedule. Similar results were found under a trace procedure in Experiment 2 when avoidance responses were reinforced 25% of the time with informational feedback stimuli. In contrast, during Experiment 3, when animals were shocked on only 25% of the trials on which they failed to respond, the level of avoidance responding during both acquisition and extinction was significantly less than it was when animals were shocked on a 100% schedule. Comparable results were found in Experiment 4 when avoidance responses during acquisition averted shock on only 25% of the trials. Thus, intermittent reinforcement contingencies involving response-contingent feedback stimuli and shock have differential effects on avoidance responding during both acquisition and extinction trials under the signaled avoidance procedure.     

Interaction between catecholaminergic and opioid systems in an active avoidance task

Male NMRI mice were given intravenous injections of the noradrenergic neurotoxin DSP4 or the vehicle 24 to 72 h prior behavioral testing. Animals were given 2 days of training on a one-way active avoidance task. Naloxone was given in one of three doses prior to training on Day 1 and Day 2 or prior to training on Day 1 only (saline was given prior to training on Day 2). There was a dose-dependent impairment of acquisition by naloxone in the vehicle-pretreated groups; 10 mg/kg naloxone produced a significant impairment of acquisition. Naloxone also modulated retention (Day 2) performance of the active avoidance task. For vehicle-pretreated mice, 1 mg/kg naloxone facilitated and 10 mg/kg naloxone-impaired performance on Day 2. DSP4 alone produced an impairment of acquisition of this task but had no effect on retention; Day 2 scores were slightly higher in the DSP4-pretreated group than in the vehicle-pretreated group. Naloxone produced somewhat different effects in DSP4-pretreated animals than in vehicle-pretreated animals. Naloxone (1 mg/kg) ameliorated the DSP4-induced impairment of acquisition; 10 mg/kg naloxone did not significantly alter the acquisition performance of this group. For the DSP4-pretreated mice that received naloxone before training on both days, the dose-response characteristics for retention scores were similar to those of vehicle-pretreated mice; 1 mg/kg naloxone was the facilitatory dose. However, for DSP4-treated mice that received naloxone before training on Day 1 only, there was a shift to the right in the effective facilitatory dose of naloxone. For these animals, 10 mg/kg naloxone but not 1 mg/kg naloxone significantly enhanced retention performance. We discuss these results in the context of a possible state-dependent modulation by naloxone in the DSP4-treated animals.     

What is both necessary and sufficient to maintain avoidance responding in the shuttle box?

To learn what maintains the frequency of shuttle box avoidance responses, male rats from the Berkeley S₁ strain, after 200 trials of standard discriminative avoidance training, were given 100 additional trials under one of four different conditions. Responding at the maximum rate was maintained when animals performed under the training conditions or when responses continued to terminate the warning signal immediately, even though shock was never given for failing to respond. In contrast, avoidance responding was reduced markedly if, and only if, trials were given in which the signal ceased to terminate immediately (i.e. it shut off either well before or well after a response). This decrement occurred even though avoidance responses continued to avert shock. Thus, under the conditions of this experiment prompt signal offset was both necessary and sufficient to maintain the occurrence of well-established shuttle box avoidance responses.     

Facilitation of a Distributed Shuttle-Box Conditioning with Posttraining Intracranial Self-Stimulation in Old Rats

Old Wistar rats (16–17 months) were trained in a two-way active avoidance task for 5 consecutive days (10 trials/day). Immediately after each training session a lateral hypothalamic intracranial self-stimulation session (ICSS group) or a sham-treatment session (Control group) was given to the animals. Long-term retention was tested 7 days after the last acquisition session. ICSS treatment led to a significant improvement in acquisition. In the long-term retention session the level of avoidance in both groups was similar to that achieved in the last acquisition session, although differences among groups failed to reach statistical significance. These results are compared with those obtained in previous experiments with young adult rats. While ICSS facilitated the process of acquisition in both young and old rats (however, it was much more powerful in young animals), further experiments are needed to elucidate whether this effect is long-lasting in old rats, as occurs in young adult subjects.     

Warning signal termination and a feedback signal may not serve the same function

Three experiments were conducted to test the possibility that a feedback signal (FS) and warning signal termination (WST), while equally reinforcing in the avoidance learning situation, reinforce through different underlying mechanisms. The first experiment showed that the reinforcing properties of an FS are reduced more than those of WST when these stimulus changes are made unreliable by the presence of shock following a CR on specified trials throughout acquisition. Experiment 2 confirmed this effect on avoidance performance when only a few punishment trials were administered following asymptotic avoidance acquisition. Experiment 3 demonstrated this effect during avoidance extinction with and without the presentation of punishment trials between acquisition and extinction performance. The results provided no support for the expectancy explanation of avoidance learning and were interpreted as consistent with the assumption that WST reinforces by permitting fear to dissipate and that the FS reinforces through fear inhibition.     

Effects of parafascicular excitotoxic lesions on two-way active avoidance and odor-discrimination

To investigate whether the parafascicular (PF) nucleus of the thalamus is involved in different learning and memory tasks, two experiments were carried out in adult male Wistar rats that were submitted to pre-training bilateral N-methyl-d-aspartate PF infusions (0.15M, pH 7.4; 1.2 microl/side, 0.2 microl/min). In Experiment 1, we evaluated the effects of PF lesions in two identical 30-trial training sessions, separated by a 24-h interval, of a two-way active avoidance conditioning. PF-lesioned rats exhibited impaired performance in both sessions, measured by number of avoidance responses. In Experiment 2, the effects of PF lesions were assessed in a training session (5 trials) and a 24-h retention test (2 retention trials and 2 relearning trials) of an odor-discrimination task. PF lesions did not significantly disrupt the acquisition or the first retention trial, which was not rewarded. However, lesioned animals' performance was clearly affected in subsequent trials, following the introduction of the single non-rewarded trial. Current data are discussed considering evidence that lesions of the PF nucleus affect learning and memory functions mediated by anatomically related areas of the frontal cortex and striatum.     

Stimulus selection in passive avoidance learning and retention: weanling, periadolescent, and young adult rats

Periadolescent rats exhibit a number of behavioral differences in comparison with younger or older animals. For instance, periadolescents tend to show enhanced acquisition of simple active avoidance tasks, but impaired acquisition of more complex appetitive and aversive discriminations. In this experiment, rats were trained on a simple passive avoidance task at one of three ages, as weanlings (25 days), periadolescents (35 days), or young adults (45 days). Training occurred in the presence of both a redundant discriminative stimulus and a specified, redundant contextual stimulus. The periadolescents did not differ from either younger or older rats in rate of learning the passive avoidance task. The retention performance of these animals was then tested following a change in either, neither, or both of the redundant cues. When a measure of performance that controls for baseline activity was used, it was observed that periadolescents were not disrupted by a change in the redundant discriminative stimulus, a cue change that clearly disrupted performance in 25- and 45-day-old animals, and tended to be more disrupted by the contextual change than younger or older rats. It is hypothesized that the alterations in performance exhibited by periadolescents may be related to an ontogenetic alteration in stimulus selection modulated by the catecholaminergic systems.     

Diazepam prevents post-training drug effects related to state dependency, but not post-training memory facilitation by epinephrine

Rats were trained and tested in a step-down inhibitory avoidance task (0.3-mA footshock). Training-test interval was 6 h. In Experiment 1, animals received, 1 h before training, an ip injection of vehicle or diazepam (2.0 mg/kg) and, 30 s after training and/or 30 min prior to testing, ip saline, epinephrine (6.25 micrograms/kg or 125.0 micrograms/kg), naloxone (0.5 mg/kg), or beta-endorphin (1 micrograms/kg). In the vehicle-pretreated animals, post-training epinephrine (6.25 micrograms/kg) and naloxone enhanced, and post-training beta-endorphin and epinephrine (125.0 micrograms/kg) reduced, retention test performance; and pretest beta-endorphin and epinephrine (125.0 micrograms/kg) reversed the latter effect and enhanced retention on their own. Diazepam lowered memory scores on its own and prevented all other drug effects with the exception of post-training facilitation by epinephrine (6.25 micrograms/kg). In previous papers it was shown that post-training facilitation by epinephrine is due to an influence on storage processes, whereas all the other drug effects described above result from the post-training establishment of state dependency to either beta-endorphin or epinephrine, and therefore to a process involving further acquisition and storage. The present findings suggest that diazepam selectively hindered the acquisition and/or storage processes involved in state dependency. This conclusion is strengthened by the findings from Experiment 2, which showed, using a classic 2 x 2 design, that diazepam itself did not induce state dependency but, rather, depressed acquisition and/or storage of the avoidance task.     

The Effects of Intra-amygdala Infusion of the AMPA Receptor Antagonist CNQX on Retention Performance Following Aversive Training

The aim of these experiments was to determine whether impaired retention performance in aversively motivated tasks, induced by blockade of amygdala AMPA receptors, is due to influences on mechanisms underlying memory retrieval or to other influences on performance. Rats received either footshock escape training (1 or 10 trials), or no foot shock, in a two-compartment straight alley and bilateral intra-amygdala infusions of the AMPA receptor antagonist CNQX (0.5 μg) were subsequently administered prior to inhibitory avoidance retention testing 8 days later. The CNQX impaired, but did not block, inhibitory avoidance retention performance as indicated by the initial latencies to enter the shock compartment. The animals were then retained in the alley until they remained in the starting compartment for 100 consecutive s and entries into the shock compartment were recorded as errors. In both the controls and CNQX-treated groups, increases in amount of original training resulted in fewer errors, indicating memory for the escape training. Furthermore, regardless of the amount of original training (i.e., 0, 1, or 10 trials), CNQX-treated groups made more errors. Other experiments examined intra-amygdala CNQX effects on reactivity to footshock, locomotor activity, and anxiety. CNQX decreased reactivity to footshock, blocked shock-induced decreases in locomotor activity, and had an anxiolytic effect in an elevated plus maze comparable to that induced by midazolam (0.5 μg). These findings suggest that intra-amygdala infusions of CNQX prior to retention testing affect inhibitory avoidance retention performance following aversive training by altering locomotor activity, reducing sensitivity to footshock, and reducing anxiety. The implications of these findings for hypotheses concerning amygdala function in aversively motivated learning and memory is discussed.     

Anisomycin infused into the hippocampus fails to block "reconsolidation" but impairs extinction: the role of re-exposure duration

Recent studies have reported new evidence consistent with the hypothesis that reactivating a memory by re-exposure to a training context destabilizes the memory and induces "reconsolidation." In the present experiments, rats' memory for inhibitory avoidance (IA) training was tested 6 h (Test 1), 2 d (Test 2), and 6 d (Test 3) after training. On Test 1 the rats were either removed from the shock compartment immediately after entry or retained in the shock context for 200 sec, and intrahippocampal infusions of the protein synthesis inhibitor anisomycin (75 microg/side) were administered immediately after the test. Anisomycin infusions administered after Test 1 impaired IA performance on Test 2 in animals given the brief re-exposure, but impaired extinction in animals exposed to the context for 200 sec. Rats with anisomycin-induced retention impairment on Test 2 demonstrated spontaneous recovery of retention performance on Test 3, whereas rats showing extinction on Test 2 showed further extinction on Test 3. The findings indicate that post-retrieval administration of anisomycin impairs subsequent retention performance only in the absence of extinction and that this impairment is temporary.     

Escape conditioning and goal punishment: Effects of acquisition trials,initial punishment trials,and CS extent

In the first of three experiments in which albino rats were given spaced shockescape trials in a straight runway, groups of 6 animals were given 6 or 24 trials followed by extinction, with or without goal-box punishment. Punishment facilitated behavior after 24 trials but did not significantly affect it after 6. Both punishment and 24 trials led to more “abrupt” extinction. In the second experiment, 6 groups of 6 animals received 6, 12, or 24 trials followed by 54 extinction trials with or without goal punishment on the first 18. All punished groups ran self-punitively, and acquisition trials effects were apparent during and after punishment. In the third experiment, buzzer extent, or duration, was manipulated, and longer extents produced stronger self-punitive effects. The results of all three experiments were interpreted in the context of presumed directive effects of aversive and conditioned aversive stimuli.     

Chronic propranolol induces deficits in retention but not acquisition performance in the water maze in mice

Agents that alter adrenergic receptors, such as "beta-blockers," also alter memory storage. However, reports suggest that beta-adrenergic receptor antagonists, such as propranolol, have conflicting behavioral effects with acute vs chronic dosing. This study was designed to evaluate the effects of chronic propranolol on retention for a spatial learning task. Adult male ICR mice were given daily injections of propranolol (2, 4, 8, or 12 mg/kg ip) or 0. 9% NaCl for 15 days prior to, and during, trials in a Morris water maze. Mice received five massed acquisition (escape) trials in each of three daily sessions, followed by a single 60-s probe trial on the fourth day. The location of the submerged platform was constant for each animal over acquisition trials, but varied across animals; starting position varied across trials. A 5 (dose) x 3 (trial blocks) mixed factorial ANOVA for escape time yielded a significant trial blocks effect only (p <.001), showing performance improving over sessions. Time spent in the target quadrant on the probe trial was shorter under all doses of propranolol when compared to vehicle group (all p <.001), indicating poorer retention of prior platform location. This effect, however, was not dose-related. Swim speed was not significantly affected by propranolol. These data demonstrate that chronic dosing with propranolol can impair retention of spatial learning, which cannot be attributed to reduced arousal or motor function.     

Models of performance in learning multisegment movement tasks: consequences for acquisition,retention, and judgments of learning

Participants learned different keystroke patterns, each requiring that a key sequence be struck in a prescribed time. Trials of a given pattern were either blocked or interleaved randomly with trials on the other patterns and before each trial modeled timing information was presented that either matched or mismatched the movement to be executed next. In acquisition, blocked practice and matching models supported better performance than did random practice and mismatching models. In retention, however, random practice and mismatching models were associated with superior learning. Judgments of learning made during practice were more in line with acquisition than with retention performance, providing further evidence that a learner's current ease of access to a motor skill is a poor indicator of learning benefit.     

Sequence-Specific Impairment of Memory Formation by NCAM Antisense Oligonucleotides

The functional role of NCAM gene expression in memory formation was studied in the one-trial passive avoidance task in day-old chicks by pretraining injections of one of three different 18-mer end-protected oligonucleotides corresponding to positions 190-, 207-, and 332- of the NCAM Ig1 domain. Twenty-four-hour-old chicks were trained by pecking at a bitter-tasting bead and tested for avoidance 30 min, 3, 8, or 24 hr later. Memory retention was significantly reduced only in the group of animals injected with the NCAM antisense corresponding to position 207- (AS-ODN-207), and only if given twice, both immediately after hatching and 12 hr before training. This antisense was without effect on the general behavior of the chicks, training or acquisition, and did not produce observable neurotoxic damage. Under such conditions amnesia was evident by 3 hr after training and lasted until at least 24 hr after training. The two other tested oligonucleotides were without behavioral effect. To control for nonsequence-specific effects of AS-ODN-207, brains from injected and trained animals were processed for Western blotting and probed using anti-NCAM, anti-L1, and anti-actin antibodies. NCAM antisense corresponding to position 207- significantly reduced the level of NCAM, whereas the level of L1 and actin remained unchanged. These results confirm our earlier conclusion that NCAM is necessary for longer term memory retention.     

Motor Learning as a Function of KR Schedule and Characteristics of Task-Intrinsic Feedback

Forty participants (age range = 18–35 years) practiced 1 of 2 versions of an aiming task (with or without spring resistance). Knowledge of results (KR) was provided to them either immediately or after a delay of 2 trials. Immediate KR led to significantly more accurate performance during the 80 trials in acquisition but significantly less accurate performance on a 40-trial retention test given 24 hr after practice. In addition, the spring version of the task was performed significantly less accurately than the no-spring version on the 24-hr retention test. Most important, a significant interaction on the 24-hr retention test revealed that performance of the no-spring version of the task, when KR had been given after a 2-trial delay, was significantly more accurate than performance of the other 3 combinations of task version and KR schedule. The results suggest that KR dependency in motor skill learning is related to familiarity with task-intrinsic feedback in addition to the schedule on which KR is presented.     

Motor learning as a function of KR schedule and characteristics of task-intrinsic feedback

Forty participants (age range = 18-35 years) practiced 1 of 2 versions of an aiming task (with or without spring resistance). Knowledge of results (KR) was provided to them either immediately or after a delay of 2 trials. Immediate KR led to significantly more accurate performance during the 80 trials in acquisition but significantly less accurate performance on a 40-trial retention test given 24 hr after practice. In addition, the spring version of the task was performed significantly less accurately than the no-spring version on the 24-hr retention test. Most important, a significant interaction on the 24-hr retention test revealed that performance of the no-spring version of the task, when KR had been given after a 2-trial delay, was significantly more accurate than performance of the other 3 combinations of task version and KR schedule. The results suggest that KR dependency in motor skill learning is related to familiarity with task-intrinsic feedback in addition to the schedule on which KR is presented.     

Paradoxical Sleep Deprivation and Sleep Recording Following Training in a Brightness Discrimination Avoidance Task in Sprague–Dawley Rats: Paradoxical Effects

Previously, we reported that posttraining paradoxical sleep deprivation (PSD) resulted in an enhancement of the subsequent avoidance performance for rats trained for 15 trials in a Y-maze brightness avoidance discrimination task. A series of experiments were conducted to try to further understand the reasons for results which were contrary to those of the bulk of the sleep-learning literature. Experiment 1 investigated the effectiveness of the PSD technique. Rats (N= 4) were sleep recorded while residing on a “swimming pool” apparatus for 24 h. Compared to their baseline values, all animals showed a very large reduction in paradoxical sleep and spent significantly more time awake. Slow-wave sleep was unchanged. In Experiment 2, proactive motor effects were tested. Rats were deprived of PS for 24 h and then tested in a hole board motor activity task. There was a slight effect of PS deprivation on the day following the PSD and no effect when the rats were retested 1 week later. Experiment 3 investigated possible proactive effects of PSD on avoidance performance. Rats exposed to PSD in the 24 h before training in the Y-maze task did not demonstrate any facilitative effect on the subsequent avoidance performance. Experiment 4 investigated the possibility that the PSD facilitative effect could be due to partial training. Rats were given 75 acquisition trials in the brightness discrimination Y-maze avoidance before being subjected to 24 h of PSD. PS-deprived animals showed superior avoidance scores compared to non-PSD controls when retested 24 h later. In Experiment 5, the same strain of rats (N= 11) were sleep recorded after exposure to a partial acquisition in a Y-maze brightness avoidance discrimination task. They were then continuously monitored for 4 consecutive days. The percent PS for the Trained rats was significantly lower than that for the Control animals. This drop in percent PS was not confined to any particular time period in the 24-h day. None of the other sleep parameters reached significance. Analyses of the present results suggest that PSD exerts its facilitative effects on posttraining consolidation processes. We present arguments suggesting that PSD can have effects opposite to those generally reported, in animals demonstrating poor avoidance abilities, in an avoidance task.     

Glucose effects on memory: behavioral and pharmacological characteristics

Recent findings indicate that post-training glucose injections can modulate memory storage for inhibitory (passive) avoidance training. Experiment I extended these findings to determine whether glucose, like other memory modulating treatments, enhances memory storage when administered after training with low footshock and impairs memory storage after high footshock training. In Experiment I, male Sprague-Dawley rats were trained in a one-trial inhibitory avoidance task using either a brief footshock (0.5 mA, 0.7 s) or slightly more intense footshock kept on until escape (0.7 mA, mean escape latency = 3.4 s). Immediately after training, each rat received a subcutaneous injection of glucose (100 mg/kg). When tested for retention performance 24 h later, the glucose-injected animals exhibited enhanced retention performance for low footshock training and impaired retention for high footshock training. Experiment II determined whether pretreatment with adrenergic antagonists blocked the effects of glucose on memory. Pretreatment with the alpha- or beta-adrenergic receptor antagonists, phenoxybenzamine, or propranolol, respectively, had no effect on acquisition or retention in animals trained with the brief footshock and did not affect glucose facilitation of that memory. In animals trained to escape footshock, phenoxybenzamine did not attenuate the amnesia produced by glucose. Propranolol-pretreated animals had impaired retention whether or not they received post-training amnestic injections of glucose; glucose had no effect on retention in these amnestic animals. These findings add further support to the view that glucose release after training and treatment may represent a physiological response subsequent to epinephrine release in modulating memory storage processing.     

Intracerebroventricular effects of angiotensin II on a step-through passive avoidance task in rats

A wealth of evidence indicates that angiotensin II (Ang II) is involved in learning and memory. However, the precise role of this peptide in these cognitive processes is still controversial, with data indicating either an inhibitory or an enhancing action. The present study was designed to further investigate the effects of intracerebroventricular injections of Ang II (0.5, 1 or 3nmol/5microl) on a step-through passive avoidance task in male adult Wistar rats. When administered pretraining, Ang II did not affect the acquisition of passive avoidance, but markedly improved avoidance performance when given before the retrieval test. The latter effect was observed in retest sessions performed up to 72h after training. Administration of the peptide five minutes after training impaired retention of inhibitory avoidance. Therefore, Ang II may exert opposite effects on passive avoidance memory according to its interference with brain mechanisms leading to the storage or retrieval of this aversively motivated task.