The effects of ECS and hypoxia on information retrieval

Seven groups of rats were trained in a passive avoidance task. All groups were tested 24 hr later to assure retention of the task. One group of animals was then administered an ECS treatment. Three groups were administered an ECS treatment under conditions which eliminate or reduce the production of hypoxia. Another group was exposed to a nitrogen atmosphere to induce hypoxia by a different method. All groups were then retested for retention of the passive avoidance task 3 and 24 hr later. The results indicate that ECS or nitrogen inhalation (both hypoxia producing treatments) produce an amnesia for the passive avoidance task at the 3 hr retest but not at the 24 hr retest. In contrast, minimizing or eliminating the hypoxic consequences of an ECS treatment does not result in a temporary amnesic effect.     

The locus coeruleus: its possible role in memory consolidation.

Three experiments were done looking at the effects on memory of discrete electrolytic lesions in the locus coeruleus of mice. In Experiment 1 mice received electrolytic lesions of the locus coeruleus immediately following training on the 1 trial inhibitory avoidance step-through task. Retention of this response, measured 48 hr later was normal, suggesting that locus coeruleus lesions per se do not interfere with the performance of this rather simple response. In Experiments 2 and 3 mice were treated exactly as in Experiment 1 except that a transcorneal ECS was administered 40 hr or 7 days after initial training and locus coeruleus lesions. Mice with locus coeruleus lesions were amnesic following a 40 hr delayed ECS treatment when tested either 8 hr or 24 hr after ECS. Mice with locus coeruleus lesions were not amnesic following a 7 day delayed ECS. These data are interpreted to suggest that the locus coeruleus is normally involved in the temporal delineation of the susceptibility period of newly formed memory. A malfunction of the locus coeruleus can result in a profound extension of the normal susceptibility period of newly formed memory to ECS produced amnesia.     

Novel experience prior to training attenuates the amnestic effects of posttraining ECS

In this article, mice were given a novel exploratory experience 1 hr prior to training on a one-trial inhibitory avoidance task or a Y-maze shock-motivated visual discrimination task. Half of the animals in each group received immediate posttraining electroconvulsive shock (ECS) delivered through implanted cortical screws. Retention was tested 24 hr later. In the inhibitory avoidance task, retention was assessed by the response latencies on Day 2. In the Y-maze, the discrimination was reversed on Day 2 and retention of the original discrimination was assessed by errors made on six reversal training trials. Comparable results were obtained in the two tasks: ECS impaired retention in controls not given the novel experience but did not affect retention in mice given the novel experience. These findings are interpreted in terms of previous evidence, which suggests that ECS-induced amnesia may be mediated by the release of brain beta-endorphin.     

Noncontingent footshock attenuation of retrograde amnesia: a generalization effect

Mice were either well trained and rendered amnesic with transcorneal electroconvulsive shock (ECS) or poorly trained on a one-trial inhibitory avoidance task and given a retention test 24 and 48 hr later. Noncontingent footshock administered either 1 hr after the training or 1 hr after the 24 hr test significantly increased retention latencies of groups which had received training and ECS, as well as those of groups which were poorly trained. These findings suggest that animals which are partially amnesic or poorly trained are able to generalize the effects of a subsequent NCFS experience to the inhibitory avoidance training task.     

Reduction of ECS produced retrograde amnesia by post-trial introduction of strychnine

Strychnine sulfate was used to reduce the amount of retrograde amnesia induced by electroconvulsive shock (ECS). Male Swiss-Webster mice were trained on the step-down passive avoidance task, given ECS and then injected intraperitoneally with either 0.1 mg/kg strychnine or saline. The animals were tested in the apparatus one to twenty-four hours later. Mice given ECS alone displayed partial memory for the training (by responding with longer latencies) if tested within two hours after training, but did not display retention twenty-four hours later. Animals given strychnine following ECS had significantly longer step-down latencies at twenty-four hours than did the saline or no injection controls. Further experiments replicated the basic results, and also showed that strychnine injections delayed two hours after the training trial attenuated ECS-induced retrograde amnesia, but that a three hour injection delay was ineffective. The results were interpreted in terms of changes in short-term and long-term memory.     

Function of ECS as a cue in retrograde amnesia in the rat

Two experiments were performed with rats to examine whether electroconvulsive shock (ECS), which is known to produce retrograde amnesia (RA), would serve as a dominant cue in the training trial. In Experiment I, after 6, 1, or 0 ECS preexposures , rats were received ECS immediately following one-trial passive avoidance training in a step through apparatus. Twenty-four h later, six ECS preexposure group showed a higher level of retention performance. Thus, the effects of ECS on RA were shown to be attenuated by the preexposure to ECS. In Experiment II, it was shown that ECS acquired a considerable amount of cue value which might produce a conditioned suppression on an off-the-baseline type procedure. These results were interpreted as that RA phenomena could be considered as a sort of retroactive conditioning where ECS served as a CS.     

Retention impairment by posttraining epinephrine: role of state dependency and of endogenous opioid mechanisms

Mice were trained in a step-through inhibitory avoidance task with a 0.6-mA, 60-Hz, 2-s footshock and were tested for retention 3 or 6 hr later. Posttraining intraperitoneal administration of a high dose (25.0 micrograms per mouse) of epinephrine (Epi) impaired retention; this effect was counteracted by another injection of the same dose of Epi given before retention testing either 3 or 6 hr after training. When administered before the 6-hr test but not the 3-hr test, however, Epi enhanced retention (i.e., above that of controls). The retention enhancement, but not the reversal of impairing effects of posttraining Epi, was antagonized by naltrexone (20.0 micrograms per mouse). Naltrexone, when administered alone, had no effect on retention when given before testing. However, posttraining administration of naltrexone produced an enhancement of retention detectable 6 but not 3 hr after training. Furthermore, posttraining naltrexone also blocked the impairing effect of posttraining Epi otherwise seen 6 hr after training. These results suggest that the impairment of retention caused by posttraining Epi is attributable to the induction of state dependency based on an Epi state. When the animals are tested 3 hr after training, this effect appears alone. But, when tested 6 hr after training, the Epi effect appears together with an opioid, presumably beta-endorphin-mediated, state dependency.     

Attenuation of experimental retrograde amnesia through pretraining administration of a dissimilar amnestic agent

Experiment 1 found that pretraining administration of electroconvulsive shock (ECS) attenuated ECS-induced amnesia of one-trial passive avoidance training in rats. Similarly, pretraining injections of cycloheximide (CXM) attenuated the amnestic effects of CXM at training. Experiment 2 demonstrated the ability of pretraining ECS to attenuate CXM-induced amnesia and pretraining CXM to attenuate ECS-induced amnesia. These studies join others in observing comparable behavioral effects of ECS-like amnestic agents and antimetabolite-like amnestic agents despite their different means of primary action. Collectively, these studies support the view that the two families of amnestic agents produce amnesia through a common mechanism.     

Learning and retention of a discriminated escape response in infant mice

Separate groups of mice received 25 training trials in a shock-escape T-maze at 7,9,11, or 13 days of age, followed by retention trials 24 hr later. During original training, all mice were trained to the goal opposite their 1st-trial choice-point turn. During the retraining sessions, half of the mice in each age group received an additional 25 trials to the same goal as original training, while the other half was trained to the goal opposite that of original training. All age groups demonstrated improved performance during training in reaching the choice point, although only mice 9 days of age and older indicated an increase in correct choice-point turns. During retraining, only the groups trained at 11 and 13 days of age showed significant effects of prior training.     

Attenuation of amnesia by hydrocortisone in the mouse

Effects of hydrocortisone on the retrograde amnesia produced by electroconvulsive shock (ECS) was studied in 228 mice. The animals were given ECS after one-trial training in a step-through apparatus, and tested for passive avoidance behavior 7 days later. The amnesic effect of ECS was absent in the animals that were injected with hydrocortisone SC prior to the administration of ECS. Hydrocortisone alone, without ECS, had no significant effect on passive avoidance. There was no indication that the hormone suppressed the ECS-induced seizure activity in the brain. The results suggest that hydrocortisone protected the animals from amnesia by acting on the brain before the onset of the disruptive action of ECS.     

Differential susceptibility to anterograde and retrograde amnesia treatments in preweanling rats

Although there have been several reports that preweanling rats and mice are relatively resistant to experimentally induced retrograde amnesia, there is virtually no information concerning susceptibility to anterograde amnesia in subjects of this age. Therefore, in the present experiment, 23-day-old rats received hypothermia either prior to, or immediately after, punishment training in an attempt to induce anterograde and retrograde amnesia, respectively. When tested 24 hr later, only those subjects given hypothermia prior to training exhibited any loss of retention. Thus these results confirmed previous evidence of resistance to retrograde amnesia in preweanling rats and further demonstrated that substantial anterograde amnesia could be obtained in these subjects. Performance of subjects tested after a 5-min retention interval revealed that the poor retention performance in subjects cooled prior to training and tested 24 hr later was not due to a learning deficit. These results are also discussed with respect to the issue of the independence of anterograde and retrograde amnesia.     

Extending the duration of ACTH-induced memory reactivation in an amnesic paradigm

The effectiveness of ACTH treatment in reversing hypothermia-induced retrograde amnesia was investigated in a passive avoidance paradigm. Subcutaneous injections of ACTH 30 min prior to a retention test attenuated the amnesia typically evidenced 24 hr after whole body cooling. Experiment 2 found no evidence for the reversal of amnesia 24 hr after ACTH treatment; however, when ACTH was combined with brief exposure to the “fear” cues previously associated with training substantial memory recovery was sustained over 24 hr. Although fear cue exposure without prior ACTH treatment also attenuated amnesia, the memory recovery was significantly less than that following the combined ACTH/cue exposure. Neither ACTH nor ACTH/cue exposure following sham-training appeared to have any consequence on performance. A final experiment replicated these findings and further suggested that the memory recovery induced by the combined ACTH/cue exposure persisted over 7, but not 14 days. It was suggested that although the combined hormone/behavioral reactivation treatment may extend the duration of ACTH-induced recovery from amnesia, a reactivated memory, like other memories, appears susceptible to ordinary sources of retention loss.     

The effects of strychnine on recently acquired and reactivated passive avoidance memories

Rats were trained on passive avoidance (PA) or were given equivalent handling and footshocks (FS) prior to injection with either strychnine (1 mg/kg IP) or saline. Twenty-four hr after injection, rats in the PA-strychnine condition took significantly more trials to learn active avoidance than did animals in any of the other conditions. In Experiment 2, the interval between PA training and the strychnine treatment was extended to 72 hr. Using this interval, retarded active avoidance acquisition occurred only when the memory of PA training was reactivated just prior to the strychnine injection. Results were interpreted as indicating that strychnine enhanced the memory of the PA training requirements, thus interfering with the acquisition of active avoidance. However, this enhancement did not appear to depend on the influence of strychnine on the consolidation of the PA memory.     

Recovery of Memory by the Glutamate NMDA Receptor Agonist D-Cycloserine Depends on the Stage of Development of Amnesia

We have previously observed that in common snails trained to an associative skill consisting of refusing a defined foodstuff, impairment of memory reconsolidation by the NMDA receptor antagonist MK-801 evokes amnesia in which the skill can be recovered by retraining at the early stage (<10 days) while retraining at the late stage does not lead to formation of the skill. In the experiments reported here, amnesia was induced with MK-801 and a reminder 24 h after training of snails to conditioned taste aversion, and the antiamnestic effects of D-cycloserine, a partial agonist of the glycine site of the NMDA receptor, were studied in the early (day 3) and late (day 12) stages. Three days after induction of amnesia, injections of D-cycloserine and a reminder of the conditioned food stimulus led to recovery of the memory; administration of D-cycloserine without a subsequent reminder was ineffective. Injection of D-cycloserine and a reminder 12 days after induction of amnesia had no effect on its development and retraining did not lead to recovery of the memory. Thus, this study is the first to show that the NMDA receptor agonist D-cycloserine influences memory recovery processes only at the early stage of development of amnesia induced by lesioning of reconsolidation processes, while the late stage of amnesia was not sensitive to this agonist.     

Development of learning and memory in mice after brief paradoxical sleep deprivation.

The effects of three hour paradoxical sleep deprivation (3 hr PSD) via the water tank procedure to produce retrograde amnesia of active avoidance and inhibitory avoidance learning was examined in mice. Results indicated no memory impairment in experimentally treated groups. An attempt was then made to induce amnesia by administering ECS immediately after 3 hr PSD thereby increasing the susceptibility of the memory trace to disruption. This procedure, however, also results in good retention. We conclude that the paradoxical sleep (PS) phase immediately after aversively motivated training is not essential for subsequent development of learning and memory. These results do not, however, detract from previously reported protracted PSD effects on memory storage processes.     

Methodological issues in drug-drug conditioning in rats: nonassociative factors in heart rate and avfail.

Sodium pentobarbital injections followed 30 min later by d-amphetamine sulfate produce an effect over trials in the form of an increase in heart rate in response to pentobarbital in relation to rats that receive the 2 drugs 24 hr apart (long-delayed control: Revusky, Davey, & Zagorski, 1989). This study found equivalent increases in heart rate in forward and backward groups in relation to a long-delayed control regardless of whether training or testing was carried out in a heart rate recording apparatus or in the home cage, which suggests that a drug interaction due to drug administrations in forward and backward groups has yet to be eliminated in accounting for the heart rate effect. Comparison of backward and long-delayed controls in a drug-drug procedure that used a taste aversion test revealed that both forward and delayed pairings can produce attenuated aversions in relation to a backward group regardless of whether the unconditional stimulus is amphetamine (Experiment 1) or lithium chloride (Experiment 2).     

Combined effects of ECS and Metrazol on passive avoidance learning

The combined effects of a non-convulsant dosage (10 mg/kg of body weight) of Metrazol and 60 min ECS were investigated in order to find out if the interaction of the two would produce an amnesic effect upon passive avoidance learning. The main group of rats was given FS, with an immediate posttrial injection of Metrazol, followed by ECS at 60 min. Four other groups were given footshock (FS) followed by saline injection. Three of these 4 groups received ECS following FS at 30, 45, and 60 min respectively, leaving one group receiving only footshock. The footshock only and 60 min ECS groups had the same mean starting and running times, indicating no amnesia with 60 min ECS. The Metrazol 60 min ECS group had a significant retention deficit, falling between the 45 and 30 min groups. The results support the consolidation disruption hypothesis of ECS induced amnesia, and are contrary to the incubation interpretation of these effects.     

Modification by environmental conditions of retrograde amnesia produced by ECS

A single ECS following one trial appetitive learning produced retrograde amnesia after 24–72 hr in rats housed individually in a colony during the ECS-retention trial interval. In animals given the same treatment procedures and housed individually in a dark chamber with a constant level of background noise, no retrograde amnesia following ECS was noted. These results suggest that varying environmental conditions during the ECS-retention interval may eliminate or enhance retrograde amnesia. Further, these deficits in retention appear to be retrieval deficits which are associated with events producing brain dysfunction and loss of retention.     

Anterograde amnesia induced by hyperthermia in rats

Anterograde amnesia (AA), forgetting of events that occur following a traumatic episode, has recently been demonstrated by using a mild decrease in temperature (hypothermia) as the amnestic agent. However, no data currently exist to indicate if an increase in body temperature (hyperthermia) might affect memory processing in a similar manner. Experiments 1 and 2 demonstrated that increasing the colonic body temperature of the rat to 3-4 degrees C or more above normal during avoidance training produced a significant retention loss when the test occurred 24 hr after training. Slight hyperthermia to 1-2 degrees C above normal did not impair retention. In Experiment 3, AA resulting from an elevation in temperature was reversed by reheating "amnestic" subjects just prior to the 24-hr test. By rapidly reversing hyperthermia immediately after the training trial with a cooling procedure, Experiment 4 demonstrated that hyperthermia-induced AA was not the result of retrograde influences of the heating treatment. Implications of these results are discussed in terms of possible retention deficits which could conceivably follow environmental heat stress or fever hyperthermia resulting from bacterial infection.     

Memory consolidation: further evidence for the four-phase model from the time-courses of diethyldithiocarbamate and ethacrynic acid amnesias

Thirty min prior to training rats in an active-avoidance task they were injected intracisternally (IC) with 3 mg diethyldithiocarbamate (DDC), a norepinephrine (NE) synthesis inhibitor. They showed complete retention of memory for about 10 min after training. Subsequently, memory decayed to the naive level over the next 80 min but reappeared later. The brain NE level fell to 50% of its normal level 30 min after the injection. 90 min later it recovered to 85% of its normal level. The dopamine level did not change. We have shown previously that brief-hypoxia causes a delayed transient amnesia. The time-course of the DDC-induced amnesia was identical. Both treatments are interpreted to interfere with Medium-Term-Memory (MTM) formation. The DDC-induced transient amnesia could be prevented by injecting 10 μg NE IC 30 min prior to training. It was concluded that NE is needed shortly after training for MTM formation. Rats were injected IC with 4 μg ethacrinic acid 30 min prior to training. They showed complete retention of memory 2 min after training, amnesia 10 min after training, complete retention 15–90 min after training and partial amnesia 3.5 hr later. Thus, ethacrinic acid appears to interfere with short-term-memory formation. These and earlier results obtained with other treatments are incorporated into a four-phase model of memory formation with parallel processing.