Acquisition Of Passive Avoidance Response Research Articles

Effects of Diazepam, Piracetam, and Mexidol on Passive Avoidance Response

Effects of the anxiolytic diazepam and nootropics piracetam and mexidol on passive avoidance conditioning (PAC) in rats were compared in experiments using a three-compartment apparatus. The latter consisted of a central, brightly lit compartment, a noxious dark compartment in which footshock was delivered to a rat, and a safe dark compartment, where the rat was not exposed to electric shock. Footshock during the acquisition of passive avoidance response in the control animals caused an abrupt increase in the latency to escape from the central compartment during testing but did not result in preference for a safe compartment. On the basis of these data on differential effects of footshock on PAC, we suggested that learning processes, which determined the motor response delay and the safe compartment preference, had a diverse associative nature. An increase in latency is associated with the classical fear conditioning regardless of the place of electric shock exposure. In contrast to this, the safe compartment preference is associated with the formation of the memory trace about the location of the footshock exposure. The use of pharmacological substances that affect fear and memory in different ways provided additional arguments in favor of the assumption about various associative processes determining passive avoidance learning. Reduction in the level of fear using diazepam decreased the latency of motor response compared to the control value but did not affect the preference for a safe compartment. In contrast, the mnemotropic properties of piracetam and mexidol increased the preference for a safe compartment without increasing the latency. These differential pharmacological effects confirm that PAC is based on the fear conditioning, which causes an increase in the latency to escape from the central compartment, and on the memory of the location of shock exposure, which provides the preference for the safe compartment.

Scopolamine-induced learning impairment reversed by physostigmine in zebrafish

In this study, the effects of scopolamine, an acetylcholine muscarinic receptor antagonist, and physostigmine, an acetylcholinesterase inhibitor, on the learning ability and memory of zebrafish were evaluated using a passive avoidance response test. The zebrafish were trained to stay in a dark compartment to avoid a weight dropping into an acryl shuttle chamber with a central sliding door. The crossing time was increased significantly, from 30.7 ± 40.8 s to 179.3 ± 27.3 s in the training session and 179.9 ± 28.0 s in the test session carried out 2 h later in the controls. When treatment with 200 μM scopolamine was administered for 1 h prior to the training session, the crossing time did not increase. The scopolamine-induced learning deficit was ameliorated by pretreatment with 20 μM physostigmine for 1 h prior to scopolamine treatment; the crossing time was similarly increased, as shown with the controls (60.9 ± 11.5 s, 130.9 ± 27.5 s, and 183.4 ± 26.6 s in the training session and 108.1 ± 23.9 s in the test session). When scopolamine treatment was administered after the training session, the crossing time in the test session was reduced significantly as compared to that noted in the third trial of the training session, which was also ameliorated by physostigmine pretreatment. These results show that scopolamine impairs both the acquisition of passive avoidance response and retention of the learned response, and that physostigmine rescues the amnesic effects of scopolamine in zebrafish.

Prolonged fear responses in mice lacking dopamine D 1 receptor

Dopamine is an important neurotransmitter involved in learning and memory including emotional memory. The involvement of dopamine in conditioned fear has been widely documented. However, little is known about the molecular mechanisms that underlie contextual fear conditioning and memory consolidation. To address this issue, we used dopamine D 1-deficient mice (D 1−/−) and their wild-type (D 1+/+) and heterozygote (D 1+/−) siblings to assess aversive learning and memory. We quantified two different aspects of fear responses to an environment where the mice have previously received unsignaled footshocks. Using one-trial step-through passive avoidance and conditioned freezing paradigms, mice were conditioned to receive mild inescapable footshocks then tested for acquisition, retention and extinction of conditioned fear responses 5 min after and up to 45–90 days post-training. No differences were observed among any of the genotypes in the acquisition of passive avoidance response or fear-induced freezing behavior. However, with extended testing, D 1−/− mice exhibited prolonged retention and delayed extinction of conditioned fear responses in both tasks, suggesting that D 1−/− mice are capable of acquiring aversive learning normally. These findings demonstrate that the dopamine D 1 receptor is not important for acquisition or consolidation of aversive learning and memory but has an important role in modulating the extinction of fear memory.

Effects of coupled perirhinal cortex and medial septal area, fimbria-fornix, entorhinal cortex tetrodotoxin inactivations on passive avoidance consolidation in the rat

In order to ascertain the rat perirhinal cortex (PC) function during early consolidation of a passive avoidance response (PAR), and to ascertain whether there are some functional interactions with the medial septal area (MSA), the fimbria-fornix complex (FF) and the entorhinal cortex (EC), PC-MSA, PC-FF, and PC-EC coupled inactivations were performed immediately after the PAR acquisition session. Anesthetized male adult Wistar rats aged 60 days were treated with stereotaxical bilateral injections of TTX (5 ng in 0.5 μl saline) in the appropriate sites. Retrieval testing was performed 48 h later. It was shown that all three coupled inactivations were followed by significant PAR disruption. It may be concluded that PC is somehow active even during the first mnemonic phase following the acquisition session, thus better defining PC mnemonic involvement chronology. These results may be taken as indicating that during initial consolidation the engram is concurrently processed in more than one septal and parahippocampal site, each of which by itself is not absolutely necessary for the final engram formation.

Effects of combined medial septal area, fimbria–fornix and entorhinal cortex tetrodotoxin inactivations on passive avoidance response consolidation in the rat

On the basis of previous experimental evidence, it has been concluded that the entorhinal cortex (EC), the fimbria–fornix (FF) complex and medial septal area (MSA) do not take part in the consolidation phase of passive avoidance response (PAR) memorization. On the other hand, a mnemonic role during consolidation of at least two of these structures has been argued, based on several considerations. In order to ascertain whether the EC and FF are still involved in PAR memorization during consolidation, the coupled fully reversible functional tetrodotoxin (TTX) inactivation of MSA, FF and EC was performed in rats having undergone a PAR training. In Experiment 1 MSA, FF and EC were inactivated pair-wise (FF and EC always bilaterally). Permanently cannulated animals were injected stereotaxically with TTX (5 ng in 0.5 μl saline) or saline (0.5 μl) immediately following PAR acquisition. It was shown that combined FF–EC inactivation induced PAR retention impairment, whereas FF–MSA and EC–MSA inactivation was not followed by amnesic effects. Having obtained a positive result, in Experiment 2 the combined FF–EC inactivation was performed at different post-acquisition delays (0.25 h, 1.5 h, 6 h), so as to assess the duration of their involvement in PAR consolidation. It was shown that only the coupled inactivation performed at the shortest post-acquisition delay was followed by amnesic effects. Thus EC and FF play a definite role during early consolidation. The results are discussed in relation to EC, FF, MSA, and hippocampal involvement in PAR memorization, as reported in previous studies, and to their connectivity.

A peculiar pattern of temporal involvement of rat perirhinal cortex in memory processing.

By means of the fully reversible tetrodotoxin inactivation technique, perirhinal cortex (PC) mnemonic function was investigated in rats trained to a passive avoidance response (PAR). It was shown that PC functional integrity is necessary during PAR acquisition, during late and very late consolidation (from 24 hr up to 192 hr after the training session), and during retrieval. An unexpected finding was that the PC was not involved in the early consolidation period. Thus the PC may play a relatively simple relay or connective role during acquisition, but its very late and very long consolidative involvement may indicate a peculiar function in consolidation and possibly in the storage of the PAR engram. The results are discussed in terms of the mnemonic characteristics of other neural sites (amygdala, hippocampus, and entorhinal cortex) involved in the same learning process.

Entorhinal cortex and fimbria–fornix role in rat's passive avoidance response memorization

The stereotaxic administration of tetrodotoxin (TTX) was employed to induce the fully reversible inactivation of the fimbria–fornix complex (FF) and of the entorhinal cortex (EC), in order to ascertain the role of these structures in the memorization of a passive avoidance response (PAR). On permanently cannulated rats TTX (5 ng in 0.5 μl saline) or saline (0.5 μl) was injected uni- or bilaterally, respectively, in the FF and in the EC, 60 min before PAR acquisition, immediately after PAR acquisition and 60 min before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that EC unilateral or bilateral pre-acquisition inactivation was followed by amnesia, while TTX inactivation in post-acquisition and pre-retrieval had no effects. Identical results were obtained by TTX administration in FF. The experimental evidence indicates that both EC and FF play a role during acquisition of PAR engram. The results are discussed in comparison with previous ones concerning dorsal and ventral hippocampus TTX inactivation effects on rat's PAR, and in relation to hippocampal and medial septal area connectivity.

Role of ventral hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response memory trace

By means of local administration of tetrodotoxin (TTX) a fully reversible functional inactivation of rat's ventral hippocampus (VH) was obtained in order to characterize the role of this structure in the memorization of a conditioned passive avoidance response (PAR). In Experiment 1, on permanently cannulated animals, TTX (10 ng in 1.0 μl saline) or saline (1.0 μl) was injected uni- or bilaterally in the VH, respectively, 1 h before PAR acquisition, immediately after PAR acquisition, and 1 h before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that both pre-acquisition and pre-retrieval VH uni- or bilateral blockades were followed by significant PAR retention impairment, while in post-acquisition only the bilateral blockade determined PAR retention impairment. In Experiment 2, on three different groups of rats, TTX (10 ng in 1 μl saline) was bilaterally administered, under general ketamine anesthesia (100 mg/kg b.w.), into the VH at different post-acquisition delays (0.25, 1.5, 6 h). Retrieval testing, 48 h after treatment, showed that post-acquisition bilateral VH blockade caused PAR impairment only when performed 0.25 h after acquisition. The results clearly indicate a role of VH during acquisition, consolidation and retrieval of PAR engram. The experimental evidence is discussed in comparison to previous results concerning TTX dorsal hippocampus blockade effects on rat's PAR and in relation to hippocampal connectivity with the medial septal area and the amygdala.

Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: a tetrodotoxin functional inactivation study

By means of local administration of tetrodotoxin (TTX) fully reversible functional inactivation of rat's dorsal hippocampus (DH) was obtained in order to define the role of this structure in the memorization of a conditioned passive avoidance response (PAR). In Experiment 1, on permanently cannulated animals, TTX (10 ng in 1.0 μ1 saline) or saline (1.0 μ1) was injected uni- or bilaterally in the DH, respectively 1 h before PAR acquisition, immediately after PAR acquisition, and 1 h before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that both pre-acquisition and pre-retrieval DH uni- or bilateral blockades were followed by significant PAR retention impairment, while in post-acquisition only the bilateral blockade determined PAR retention impairment. In Experiment 2, on three different groups of rats, TTX (10 ng in 1 μ1 saline) was bilaterally administered, under general ketamine anesthesia (100 mg/kg), into the DH at different post-acquisition delays (0.25, 1.5, 6 h). Retrieval testing, 48 h after treatment, showed that post-acquisition bilateral DH blockade caused PAR impairment only when performed 0.25 or 1.5 h after acquisition. The results indicate a well defined mnemonic role of DH during the acquisition, consolidation and retrieval of PAR engram. The experimental evidence is discussed in relation to other reports and to DH connectivity with the medial septal area and the amygdala.

Amnesic Effects of Preacquisition, Postacquisition, or Preretrieval Tetrodotoxin Administration into the Medial Septal Area on Rat's Passive Avoidance Memorization

By means of local administration of tetrodotoxin (TTX) fully reversible functional inactivation of the medial septal area (MSA) of the rat was obtained in order to define the role of this structure in the retention of a conditioned passive avoidance response (PAR). In permanently cannulated animals, TTX (5 ng in 0.5 μl saline) or saline (0.5 μl) was injected in the MSA. TTX or saline was administered to six different groups of rats, respectively 1 h before PAR acquisition, immediately after PAR acquisition, and 1 h before PAR retrieval, performed 48 h after the acquisition trial. It was shown that MSA preacquisition and preretrieval TTX injections were followed by significant PAR retention impairment, while postacquisition TTX administration had no effect on PAR retention. The results indicate a well-defined mnemonic role of MSA during the acquisition and retrieval periods but not during the consolidation of PAR engram. The experimental evidence is discussed in relation to other reports and to MSA connectivity with other subcortical structures.

Minaprine cancels scopolamine effects on the rat's acquisition of passive avoidance responses in two multitrial paradigms

The antiamnesic activity of minaprine has been studied in male Wistar rats. Two multitrial paradigms were employed: the light-dark box test (aversive stimulus: 0.6-mA foot-shocks) and the tail-handling test (aversive stimulus: manual tail-handling). In both paradigms, intraperitoneal scopolamine administration 30 min before testing significantly impaired the acquisition of the passive avoidance conditioned response. There were no significant differences in either paradigm between control rats and those to whom scopolamine and minaprine were simultaneously administered. These results show that minaprine fully protects the acquisition process of conditioned responses against scopolamine impairment not only in one-trial tests but also in multitrial paradigms. The effects of minaprine in reversing memory deficits are discussed in relation to its stimulating activity on central cholinergic systems.

Systemically administered N-methyl-D-aspartate interferes with acquisition of a passive avoidance response in rats

The effect of several doses of systemically administered N-methyl-D-aspartate (NMDA) was studied on step-through passive avoidance (PA) retention in rats. Retention of single trial PA was significantly reduced by preacquisition (30 minutes) doses of NMDA (3, 10, 30, and 50 mg/kg SC). Preacquisition amnesia was found when NMDA (30 mg/kg SC) was administered between two and 60 minutes. At shorter and longer pretreatment times (0.5 and 180 minutes) NMDA (30 mg/kg SC) did not disrupt retention testing. Across the same dose range and pretreatment times, NMDA failed to interfere with PA retention when given after acquisition or before retention testing. The results suggest that systemic NMDA administration can interfere with the acquisition of PA response but does not alter consolidation of information or retrieval.

Effects of prenatal administration of phencyclidine on the learning and memory processes of rat offspring.

The effects of prenatal administration of phencyclidine (PCP) on the learning and memory processes of rat offspring were investigated at doses below the level for producing malformations. The offspring prenatally treated with PCP (10 or 20 mg/kg) on days 7 to 17, as well as on days 7 to 21 of gestation, showed disruption of the acquisition of passive avoidance response and pole-climbing avoidance response at the ages of 4 and 7 weeks, respectively. The brain weight of the offspring prenatally treated with PCP was significantly decreased. These results suggest that prenatal PCP administration impairs learning and memory processes of passive and active avoidance tasks and that more attention should be given to the developmental toxicity of PCP.

Impairment of Memory and Changes in Neurotransmitters Induced by Basal Forebrain Lesion in Rats

AbstractThe effect of bilateral electrolytic lesioning of the anterior and posterior parts of the basal forebrain (8F) on learning behavior and changes in neurotransmitters in the central nervous system was investigated in rats The posterior BF lesion caused more severe impairment than the anterior BF lesion in the acquisition of conditioned avoidance response in a two-way shuttle box. A severe deficit in acquisition of passive avoidance response was produced by the posterior BF lesion Choline acetyhransferase (CAT) activity was decreased significantly in the parietal cortex but not in the occipital cortex in anterior BF-lesioned rats. However, it was not decreased in posterior BF-lesioned rats The contents of monoamines in the hippocampus was decreased more significantly by the posterior BF lesion than by the anterior BF lesion. These results suggest that the impairment of memory in posterior BF-lesioned rats may be related mainly to monoaminergic function rather than to cholinergic deficit.

Age-related changes in learning and memory in the senescence-accelerated mouse (SAM)

Age-related changes in learning ability were studied in senescence-accelerated mice (SAM) reared under specific pathogen-free (SPF) conditions. SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) showed an age-associated increase in spontaneous motor activity (SMA) compared with SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain) in a novel environment when the activity was measured in the light period, although there was no significant difference in the dark period. In observations of the circadian rhythm of SMA, SAM-P/8 showed a significant increase in diurnal SMA. In SAM-P/8 mice, the acquisition of passive avoidance response was slightly but significantly impaired even at 2 months of age, compared with SAM-R/1 control; the impairment became obvious with aging. In a one-way active avoidance task, SAM-P/8 did not show any impairment in the acquisition of avoidance response at 2 and 4 months of age. However, significant impairment was observed in SAM-P/8 at 12 months of age. The impairments of avoidance tasks were not due to a decrease in shock sensitivity, as indicated by no significant change in the flinch-jump threshold. In a water-filled multiple T-maze task, there was no difference in the number of errors between the two groups. With regard to the performance time to reach the goal, however, SAM-P/8 showed a mild prolongation at 2 months of age, and the prolongation became marked with advancing age. Furthermore, SAM-P/8 showed an age-related increase in the latency to escape onto the hidden platform in the Morris water task as compared with the control mice, whereas a slight but significant impairment was observed even at 2 months of age. These results indicate that SAM-P/8 shows age-related deterioration of ability in learning and memory, and the two factors of genetic strain difference and acceleration of aging are likely to be involved in the deterioration observed in SAM-P/8. Also, it is suggested that SAM-P/8 may be useful as an experimental animal model for senile memory impairment in humans.

Lesioning of the rat basal forebrain leads to memory impairments in passive and active avoidance tasks

Effects of the bilateral electrolytic lesioning of the basal forebrain (BF), including the ventral globus pallidus, on passive or active avoidance tasks, were studied in male Wistar rats. A severe deficit in acquisition of passive avoidance response was produced by the lesioning in the posterior level of BF. The retention of the passive avoidance response was markedly disrupted with post-training lesioning. Time-dependent but only slight recovery from the memory impairments was observed in the passive avoidance task given 4,8 or 16 weeks after BF lesions. The acquisition of active avoidance response using a two-way shuttle ☐ was also disturbed by BF lesioning. Retention of active avoidance response was clearly impaired by post-training lesions of the BF. The BF lesioned rats gradually acquired the passive avoidance performance when trained repeatedly at 24- or 48-h intervals, by giving a foot shock in case of avoidance failure. Extinction of the acquired passive avoidance response rapidly occurred in the BF lesioned rats. Furthermore, neurotoxic lesions of BF with kainic acid produced a significant impairment in acquisition of passive avoidance response. These results suggest that bilateral BF lesions impair the acquisition and retention of passive or active avoidance response, and that these impaired rats may be useful as an experimental model for Alzheimer's disease and senile dementia.

The effect of posttrial ECS and footshock on the acquisition of a nonshock passive-avoidance response

Experiment 1, with a 2 by 2 factorial design of training/no training, ECS/no ECS, investigated the effect of ECS on the acquisition of a one-trial nonshock passive avoidance response. Results indicated passive-avoidance learning in trained Ss and that ECS produced nearly complete retrograde amnesia (RA) for the response. Experiment 2, using the same design and procedure, investigated the effect of posttraining footshock (FS) on the acquisition of the passive-avoidance response. Results indicated passive-avoidance behavior for groups receiving training and no FS, training and FS, and no training and FS. There was no evidence of RA produced by FS.