Retrograde Amnesia In Rats Research Articles

Neuropeptide cyclo-L-prolylglycine counteracts scopolamine-induced long-term memory impairment in rats in the novel object recognition test

Background. Cyclo-L-prolylglycine (CPG) was designed and synthesized at the V.V. Zakusov as a topological analogue of the classical nootrop piracetam and was further identified as an endogenous compound. Previously, the nootropic effect of CPG was revealed in a model of retrograde amnesia in rats induced by electroconvulsive shock in the passive avoidance test (PAT).Objective. The aim of the present study was to investigate the nootropic effect of CPG under more physiological conditions in the absence of strong stressors.Methods. Amnesia in rats was modeled by intraperitoneal (ip) administration of scopolamine at a dose of 2 mg/kg. CPG was administered ip at doses of 0.1 and 1.0 mg/kg 15 minutes after scopolamine. Short- and long-term memory were recorded in the novel object recognition test.Results. It was found that scopolamine disrupted only the long-term memory of rats. CPG at a dose of 0.1 mg/ kg almost completely counteracted this impairment. CPG by itself had no effect on memory at both doses studied.Conclusion. Thus, CPG exhibits nootropic activity not only in the aversive conditions of the PAT and electroconvulsive shock-induced amnesia, but also in the neutral situation in the novel object recognition test, when the amnesia was caused by the administration of scopolamine.

AM251, a selective antagonist of the CB1 receptor, inhibits the induction of long-term potentiation and induces retrograde amnesia in rats

Long-term potentiation (LTP) has a long history as putative mechanism of memory formation, specially in the hippocampus, a structure essential for memory formation. Endocannabinoids are one of the endogenous systems that modulate this plasticity event: the activation of hippocampal CB1 receptors may inhibit local GABA release. Here, we have studied both (1) the role of the selective CB1 antagonist AM251 upon LTP induction in a hippocampal slice preparation, and (2) the effect of its intrahippocampal administration in the step-down inhibitory avoidance (IA) and the open field habituation tasks (OF). Standard extracellular electrophysiology techniques were used to record field excitatory postsynaptic potentials from the dendritic region of CA1 neurons in response to a high frequency stimulation of Schaffer's collaterals; a micropipette ejected 0.2 μM of AM251 (in DMSO/PBS) 2 min before the stimulus: LTP was induced and lasted more than 30 min in the control, but not in the AM251-treated group. Immediately after training, either in IA (footshock, 0.5 mA) or OF, animals received a bilateral infusion of 0.55 or 5.5 ng/side of AM251 or its vehicle in the CA1 region, and test was performed 24 h later. AM251 has caused a significative decrease in the test step-down latency when compared to the control group, but no differences were detected in the OF task, including the number of crossings, i.e., there were no motor effects. The LTP supression could be caused by AM251 acting over GABAergic interneurons that modulate the LTP-bearing glutamatergic neurons. Endocanabinoids would then be the natural dis-inhibitors of local plasticity in the dorsal hippocampus, and the amnestic action of AM251 would be due to a disruption of this endogenous modulatory system.

Seahorse wins all races: Hippocampus participates in both linear and non-linear visual discrimination learning

Consistent with configural/conjunctive theories of the hippocampus, we report that rats trained on the non-linear transverse patterning discrimination problem (A+ versus B−, B+ versus C−, and C+ versus A) displayed retrograde amnesia when the hippocampus was later damaged. They also failed to relearn the solution to this problem. Damage to the hippocampus following training also produced retrograde amnesia in rats trained on a set of elemental discrimination problems (A+ versus B−, C+ versus D−, and E+ versus F−) that could be solved based on the associative strengths of the individual choice cues. However, in contrast to transverse patterning, rats easily relearned and retained these elemental problems and learned a new set of elemental problems after the damage. These results support two theoretical conclusions: (a) elemental discriminations can be learned by both a system that depends on the hippocampus and a system that does not require the hippocampus, and (b) in the intact animal these two systems competitively interact with the hippocampal-dependent system inhibiting memory formation by the extra-hippocampal system.

Retrograde amnesia in rats with lesions to the hippocampus on a test of spatial memory

The present study examined remote spatial memory in a test that spans several months to determine whether remote memories are spared relative to more recent ones, as predicted by models of memory consolidation. At 3, 6 or 12 months of age, groups of rats received forced-choice training as to the location of food reward in a cross maze. At 12.5 months, rats received bilateral neurotoxic lesions to the hippocampus or a control surgical procedure and 2 weeks later their memory for the spatial location was tested. Their performance was compared to that of rats with hippocampal or control lesions with no prior training on several measures of savings. The hippocampal group with no pre-training, as expected, was severely impaired in learning the location of the food reward. Compared to this group, rats with hippocampal lesions that were pre-trained consistently performed better at the shortest training–surgery interval but not at the longer ones. That is, rats with hippocampal lesions exhibited retrograde amnesia at all training–surgery intervals and a forgetting curve that paralleled that of the control groups. The results were interpreted within a framework that distinguishes between relational and associative context, and as providing evidence that the hippocampus is necessary for the retention and retrieval of memories that are bound to relational context, regardless of the age of the memory.

Effect of stimulus intensity and number of treatments on ECS-related seizure duration and retrograde amnesia in rats.

Animal models are frequently used to generate and test hypotheses about amnesia resulting from electroconvulsive therapy (ECT). Although many predictors of ECT-induced amnesia are known, their relative effects have been inadequately researched in the context of the animal models. We sought to determine the relative retrograde amnestic effects of electroconvulsive shock (ECS) stimulus intensity (dose) and number on strong memories in rats. We also sought to identify dose-dependent ceiling amnestic effects, if any. Adult rats (n = 144) were overtrained in a passive avoidance task using a step down apparatus. The rats were then randomized in a factorial design to receive one, two, or three once-daily bilateral ECS at 0-mC (sham ECS), 30-mC, 60-mC, 120-mC, or 180-mC doses. Recall of the pre-ECS training was assessed 1 day after the last ECS. Retrograde amnesia was observed only in rats that received 3 ECS; dose-dependent amnestic effects did not emerge. Higher stimulus intensity was associated with a small (13%) but significant increase in motor seizure duration, but only at the first ECS; stimulus intensity did not influence the attenuation of seizure duration across repeated occasions of ECS. With bilateral ECS, the number of ECSs administered is a more important variable than the ECS dose in weakening a strong, recently acquired, noxious memory; this finding may have important clinical implications. Higher stimulus intensity marginally increases motor seizure duration at the first ECS but does not influence the decrease in seizure duration across repeated ECSs.

The Effects of Pretraining and Reminder Treatments on Retrograde Amnesia in Rats: Comparison of Lesions to the Fornix or Perirhinal and Entorhinal Cortices

The present experiment examined the effects of pretraining and reminder treatments on the retention of a nonrelational odor-guided digging task following lesions to the hippocampal formation (i.e., fornix) or parahippocampal region (i.e., perirhinal and entorhinal cortices). The results showed that fornix-lesioned rats and control rats had good retention of the task and did not differ from each other; however, perirhinal- and entorhinal-lesioned rats were severely impaired and differed from fornix and control rats. The present experiment found no attenuation of amnesia following pretraining, which may be due to the lesion technique employed and the size of the resulting lesions. However, the experiment found a significant difference in performance following a reminder treatment, even in the severely impaired perirhinal- and entorhinal-lesioned group.

Memory protective effect of indomethacin against electroconvulsive shock-induced retrograde amnesia in rats

Background: Nonsteroidal antiinflammatory drugs (NSAIDs) have been suggested to retard cognitive decrements in patients with Alzheimer’s disease. We postulated that NSAIDs also may protect acute disruption of memory. Methods: We studied the effect of indomethacin (4 mg/kg/day) administered daily for 19 days on retrograde amnesia induced by two once-daily electroconvulsive shocks in rats. Results: Indomethacin produced statistically significant prolongation of recall latency in a passive avoidance task using a step-down apparatus. Conclusions: Our study suggests that NSAIDs may prevent memory disruption through other mechanisms apart from attenuating chronic inflammation. In patients receiving electroconvulsive therapy, as in those diagnosed with Alzheimer’s disease, antiinflammatory drugs may hold promise in the attenuation of cognitive impairments.

Anterograde and retrograde amnesia in rats with large hippocampal lesions

A test of socially acquired food preferences was used to study the effects of large lesions to the hippocampal formation (HPC) on anterograde and retrograde memory in rats. In the anterograde test, rats with HPC lesions normally acquired the food preference but showed a faster rate of forgetting than control groups. When the food preference was acquired preoperatively, HPC groups exhibited a temporally graded retrograde amnesia in which memory was impaired when the preference was acquired within 2 days of surgery but not at longer delays. The results support the traditional theory that the HPC contributes to the consolidation of newly acquired information into a durable memory trace that is represented in other brain areas. Consistent with this view, the results indicate that, once a memory trace is consolidated, the HPC does not participate in its storage or retrieval. The possibility is considered that extrahippocampal areas in the medial temporal lobe are needed to maintain a memory trace throughout its existence.

Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks.

We review evidence from experiments conducted in our laboratory on retrograde amnesia in rats with damage to the hippocampal formation. In a new experiment reported here, we show that N-methyl-D-aspartate (NMDA)-induced hippocampal damage produced retrograde amnesia for both hidden platform and two-choice visible platform discriminations in the Morris water task. For both problems there was a significant trend for longer training-surgery intervals to be associated with worse retention performance. Little support is offered by our work for the concept that there is a process involving hippocampal-dependent consolidation of memories in extrahippocampal permanent storage sites. Long-term memory consolidation may take place within the hippocampus. The hippocampus may be involved permanently in storage and/or retrieval of a variety of relational and nonrelational memories if it was intact at the time of learning, even involving information which is definitely not affected in anterograde amnesia after hippocampal damage.

Retrograde amnesia in rats with dorsomedial thalamic damage

The present research addresses the effects of dorsomedial thalamic lesions on remembering a delayed alternation problem learned before damage. Male rats were trained on a delayed alternation task. Successful performance of the test first required learning of the general principle that Go and No Go trials alternate with each other and, second, in every trial, recalling the specific consequences of the responses in the previous trial after a relatively short or long interval. The animals which had reached the learning criteria were paired by the learning level shown during the training and assigned semi-randomly to one unoperated control and one dorsomedial thalamic lesioned group. Lesions of the dorsomedial nucleus of thalamus produced a moderate and transient impairment of remembering of the delayed alternation learned before the damage for delays ranging from 0 to 40 s, and a severe impairment of the postoperative performance when delays were increased to 80 s. Detailed analysis of the animals' performance throughout the postoperative retraining confirms the role of the dorsomedial nucleus of the thalamus in memory and suggests that this thalamic region plays a role in recalling specific response-related events. Further research concerning the extension of retrograde amnesia associated with thalamic damage and the nature of the memory loss is proposed as necessary.

Glucose administration attenuates hypothermia-induced retrograde amnesia in rats in a time- and dose-dependent manner

It is well established that posttraining administrations of glucose enhance memory in a time- and dose-dependent manner. More recently, glucose has also been found to attenuate scopolamine-induced anterograde amnesia, displaying the same time- and dose-response characteristics (Stone et al., 1988). In the present study, the use of glucose as an agent for alleviation of hypothermia-induced retrograde amnesia was examined. In each experiment, animals were given a single trial of passive avoidance conditioning. Retrograde amnesia was induced through hypothermia immediately following training. All injections were given immediately following hypothermia treatment, and tests for fear retention were administered 24 h following training. In Experiment 1, the dose-response effects of glucose (10, 100, or 400 mg/kg) were examined; in Experiment 2, the time-dependent effect of 100 mg/kg of glucose administered immediately, 1, or 2 h after hypothermia was examined. The results show that glucose injections attenuate retrograde amnesia in both a dose- and time-dependent manner. These results coincide with the growing body of evidence supporting the memory-modulating effects of glucose.

Concussion-induced retrograde amnesia in rats

Three experiments were conducted to investigate the characteristics of retrograde amnesia (RA) induced by concussion in rats. In Experiment 1, rats receiving experimental concussion shortly after training in a single punishment trial exhibited severe forgetting on a retention test 48 h later. In the second experiment, rats receiving a concussion within 6 h after training showed severe RA, while those receiving concussion one day to five days after training exhibited progressively weaker amnesia. In Experiment 3, amnesic animals in one group received pretest noncontingent foot shock as a reminder treatment. This pretest cue significantly increased the cross-through latency, thus indicating a reduction in the memory deficit resulting from concussion. These results suggest that experimental concussion can be an effective method to induce retrograde memory loss in rats; that the RA caused by concussion is time-dependent; and that concussion-induced RA can be alleviated by a pretest cue,indicating that the underlying mechanism of concussion-induced RA is more likely to be a retrieval deficit than a consolidation failure.

Nootropic correction of disturbances in learning and memory caused by superhigh frequency electromagnetic radiation

Superhigh frequency electromagnetic radiation of low intensity produces retrograde amnesia in rats tested for passive avoidance conditioning. Oxiracetam and aniracetam completely prevent the amnestic action of electromagnetic radiation, while nooglutil, piracetam, and centrophenoxine markedly weaken it. It is postulated that pyrrolidone-derived nootropics can be used for the pharmacological correction of disturbances in learning and memory caused by superhigh frequency electromagnetic radiation.

Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions assessed with the fear-potentiated startle paradigm.

Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions assessed with the fear-potentiated startle paradigm.

Lack of a temporal gradient of retrograde amnesia in rats with amygdala lesions assessed with the fear-potentiated startle paradigm.

It is well known that lesions of the hippocampal formation produce a temporally graded retrograde amnesia for certain types of memory. A similar pattern of results has been reported with amygdaloid lesions in avoidance learning (K.C. Liang et al., 1982). The present study examined the effects of posttraining amygdaloid lesions using a Pavlovian conditioning task, fear-potentiated startle, in which the amplitude of the acoustic startle reflex is increased when elicited in the presence of a cue (e.g., a light) previously paired with footshock. Electrolytic lesions of the amygdala given either 6 or 30 days after training blocked the expression of potentiated startle, indicating no temporal gradient of amnesia over these intervals in this paradigm. The effects of amygdaloid lesions on different measures of aversive learning are discussed.

Anterograde and retrograde amnesia in rats with dorsal hippocampal or dorsomedial thalamic lesions

The present research was concerned with anterograde and retrograde memory for a socially transmitted food preference in rats with lesions to the dorsal hippocampus or dorsomedial thalamus, and operated controls. In Expt. 1, food-preference training was administered postoperatively and memory was tested following various delays. Both lesioned groups acquired the preference normally, but rats with hippocampal lesions displayed a rapid rate of forgetting that indicated significant anterograde amnesia. In Expt. 2, the food preference was acquired at different times preoperatively and retrograde memory was tested postoperatively. Both lesioned groups exhibited loss of memory when training immediately preceded surgery, but only rats with hippocampal lesions displayed a temporally-graded retrograde amnesia. The results confirmed the differential effects of hippocampal and thalamic lesions on memory performance. It was suggested that memory loss following thalamic lesions was related to factors associated with original learning, whereas the pattern of hippocampal amnesia reflected disruption at a later stage in the learning process.

Role of ACTH in recovery from retrograde amnesia induced by hypothermia in rats.

The present investigation assessed whether increased congruency between ACTH state present shortly after training and that at testing contributed to memory recovery. If recovery were related to an increased correspondence between internal state present after training and that at testing, then suppressing ACTH release should block memory recovery. This was the hypothesis that was examined in the present investigation. Specifically, animals were trained on a passive avoidance task, administered hypothermia (the amnestic agent) and, shortly prior to testing, given treatments known to be effective in reversing memory loss induced by hypothermia. Before training (Experiment 1) or testing (Experiment 2) animals were injected with either dexamethasone (an agent that suppresses ACTH release) or saline. Results, in general, indicated that when ACTH release was suppressed, a blunted recovery effect was obtained. This reduction in the extent of memory recovery was observed when ACTH was suppressed either at training or at testing. These data are interpreted as providing support for an ACTH-related, state-dependent retention mechanism contributing to recovery from hypothermia-induced retrograde amnesia in rats.

Marijuana intoxication in rats: interruption of recent memory and effect on brain concentration of delta 9-tetrahydrocannabinol.

Rats exposed to marijuana smoke injected into a chamber immediately after passive avoidance training, showed a significant failure to perform the conditioned avoidance response 24 hr. later. A delivered dose of marijuana resulted in appreciable concentrations of its major behaviorally active metabolite, Δ9-tetrahydrocannabinol (Δ9-THC) in the absence of gross signs of intoxication, 24 hr. later. The greatest regional brain concentration of Δ9-THC occurred in the hippocampus, a region usually associated with memory trace processing and retention. The present study demonstrates that (1) marijuana intoxication can produce a retrograde amnesia in rats and (2) the amnesic effect is likely to depend upon Δ9-THC accumulation in the hippocampus and is probably not dependent upon the post-training intoxication state.

The effect of somatostatin, its fragments and an analog on electroconvulsive shock-induced amnesia in rats

In the present study the effects of intracerebroventricularly /icv/ administered somatostatin /linear and cyclic/, soma ostatin3–6, somatostatin7–10 and des AA1,2,4,5,12,13 /D-Trp 8/ somatostatin /ODT8-SS/ were investigated on electroconvulsive shock /ECS/-induced retrograde amnesia in rats. The ECS significantly decreased the foot shock-induced avoidance latency, and thus caused retrograde amnesia. Somatostatin /linear and cyclic/ in a dose of 0.6 nM had no action on the ECS-induced retrograde amnesia, while in doses of 3 nM and /cyclic only/ 6 nM it significantly prevented it. Somatostatin3–6, somatostatin7–10 and ODT8-SS in doses of 0.6, 3 and 6 nM had no effect on the ECS-induced amnesia. These results indicate that the whole sequence of the original somatostatin molecule is needed to block the ECS-caused retrograde amnesia.

A new nootropic aniracetam : its prevention of scopolamine-induced retrograde amnesia and its possible action mechanisms

An anti-amnesic agent, aniracetam, significantly prevented scopolamine-induced retrograde amnesia in rats in a passive avoidance situation at 50 and 100 mg/kg p.o. Aniracetam (50 mg/kg p.o.) alone did not change deoxy-D-glucose utilization rate in 102 cerebral nuclei and areas in rats, but the agent (10 and 50 mg/kg p.o.) significantly and selectively prevented the scopolamine-induced decrease in 13 and 19 nuclei, respectively. In most of these nuclei,pre-synaptic choline acetyl-transferase activity is known to be decreased in Alzheimer patients, and the two ascending activating systems (the retículo-thalamo-neocortex system and hypothalamo-archi /paleocortex system) reported to be involved in memory and learning processes include the nuclei within.