Retention Of Passive Avoidance Response Research Articles

Nootropic Activity of Extracts from Wild and Cultivated Alfredia Cernua

Antihypoxic and nootropic activities of extracts from aerial parts of wild and cultivated Alfredia cernua (L.) Cass. were studied on the models of pressure chamber hypoxia, open field test, and passive avoidance conditioning. The extracts of Alfredia cernua promoted retention of the orientation reflex and passive avoidance conditioned response and normalized orientation and exploratory activities disordered as a result of hypoxic injury. The efficiency of the extracts was superior to that of piracetam by the effect on retention of passive avoidance response throughout the greater part of the experiment. Nootropic activity of cultivated Alfredia cernua was not inferior to that of the wild plant.

Learning and memory retention in MAO A knockout mice

Transgenic Tg8 mice provide an experimental model of selective lack of the gene encoding monoamine oxidase A (MAO A), and correspond to analogous human genetic pathology found in a Dutch family. To investigate the possible consequences of the effect of the lack of a major enzyme in serotonin and catecholamine metabolism on cognitive functions, MAO A-deficient mice were subjected to a passive avoidance task. Significant differences in the learning ability and in the retention of passive avoidance response between Tg8 mice and the wild-type mice C3H/HeJ were found. MAO A-deficient mice demonstrated increased step-through latency and a longer retention of memory trace for 11 experimental days as compared to wild-type mice. We found that Tg8 mice are more resistant to detention-induced amnesia and show better social memory in social recognition test than C3H mice. The findings show an enhancement of learning and memory retention in the MAO A-deficient mice.

Amnesia induced by β-amyloid fragments is counteracted by cannabinoid CB 1 receptor blockade

Administration of drugs activating cannabinoid CB 1 receptors in the brain induces memory deficit in rodents, and blockade of these receptors may restore memory capacity in these animals. Central administration of β-amyloid or β-amyloid fragments may also lead to memory disturbances. This study was undertaken to study the involvement of cannabinoid CB 1 receptors in amnesia induced by β-amyloid fragments in mice tested in a step-through passive avoidance paradigm. Pre-training intracerebroventricular (i.c.v.) injection of β-amyloid fragments, β-amyloid peptide-(25–35) (4, 8 or 16 nmol/mouse) or β-amyloid peptide-(1–42) (200, 400, 800 pmol/mouse) 7 days prior to the learning trial reduced in a dose-dependent manner the retention of passive avoidance response. This effect was observed in two retention tests, 1 and 7 days after the learning trial. The two β-amyloid fragments showed similar potency in reducing retention of passive avoidance behavior. This effect was counteracted by a single intraperitoneal (i.p.) injection of the cannabinoid CB 1 receptor antagonist, N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H-pyrazole-3-carboxamide hydrochloride (SR141716A, 1 mg/kg), made 30 min prior to the second retention test. The injection of SR141716A per se did not affect memory capacity of mice. The i.c.v. administration of β-amyloid peptide-(25–35) (8 nmol/mouse) or of β-amyloid peptide-(1–42) (400 pmol/mouse) made 30 min prior to the learning trial failed to affect the retention capacity of mice as measured 1 and 7 days later. Also, the i.p. injection of SR 141716A (1 mg/kg) made 30 min prior to the learning trial did not influence the behavioral response of mice injected with β-amyloid peptide-(25–35) (8 nmol/mouse) or of β-amyloid peptide-(1–42) (400 pmol/mouse) 7 days prior to the learning trial. These results show that β-amyloid fragments induce a dose-dependent memory deficit. Their effect on memory retention depends upon the time of administration and seems to involve cannabinoid CB 1 receptors in the brain.

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.

Effects of reversible inactivation of the median raphe nucleous on passive avoidance learning in rats

Involvement of median raphe nucleous (MRN) in acquisition, consolidation and retrieval of passive avoidance response (PAR) was investigated with functional suppression of this area by lidocaine (LID). Rats carrying a chronically implanted cannula aimed at the MRN were trained on a stepthrough passive avoidance task and intra median raphe nucleous injection of LID or saline 5 min before acquisition trial or 5, 90 and 360 min after acquisition trial or 5 min before the retrieval test. LID injected 5 and 90 min after the acquisition trial significantly enhanced avoidance of the dark compartment in comparison with the control group injected with saline. PAR was not affected by LID injected 360 min after acquisition or 5 min before acquisition trial. PAR significantly increased in LID injected 5 min before retrieval test group comparison with the control group. Step-through latency of ndive rats was not affected by MRN blockade. The results indicate that the MRN contributes to PAR consolidation at least 90 min after acquisition and involve in PAR retention. It is concluded that functional ablation of the MRN may disrupt inhibitory actions of MRN projections to sub-cortical circuits participating in PAR learning.

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.

EFFECTS OF ACUTE OR CHRONIC ADMINISTRATION OF RISPERIDONE ON MOTOR AND SEXUAL BEHAVIOR OF MALE RATS

A number of experiments were carried out to explore the behavioral profile of a novel antipsychotic, risperidone, after acute or chronic administration, in a dose range of 0.1–10mgkg−1. This drug did not affect the acquisition and retention of avoidance behaviors in a dose of 0.1mgkg−1, either after acute or chronic administration. Higher doses induced a inhibited acquisition and a facilitated extinction (only after chronic treatment) of active avoidance behavior, but no significant effect on the retention of passive avoidance responses. In contrast, haloperidol inhibited the acquisition and facilitated the extinction of active avoidance behavior, and reduced the retention of passive avoidance reaction at the dose of 0.1mgkg−1injected either acutely or chronically. Ambulation and rearing of rats rated in an open field was increased by risperidone injected acutely at the dose of 1mgkg−1. Under the same experimental conditions, grooming appeared to be reduced. In the same test, acute or chronic haloperidol 1 or 10mgkg−1inhibited all behavioral items. Furthermore, in contrast to haloperidol, the acute or chronic administration of risperidone in a dose range of 0.1–10mgkg−1did not substantially induce catalepsy and did not affect apomorphine-induced stereotypies. Also, the dose of 0.1mgkg−1induced a facilitation of male sexual behavior by increasing the frequency and reducing the latency of mountings, intromissions and ejaculations, while haloperidol 1 or 10mgkg−1inhibited this behavior.These findings suggest that the pharmacological profile of risperidone differs from that of classical neuroleptics, like haloperidol, probably due to different mechanism or site of action.

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.

Behavioral and endocrine effects of growth hormone administration in aged female rats.

Growth hormone (GH) secretion declines during normal aging along with reproductive activity in mammalian species. Various behavioral changes also occur in aged animals. In these experiments we have studied the effects of GH administration on behavioral and endocrine alterations exhibited by aged (18 months old) female rats of the Sprague-Dawley strain. Animals were selected showing at least 2 weeks of cornified vaginal smears (constant estrous) and treated with GH (0.1 mg/kg SC) daily for 8 weeks. Vaginal smears performed during the drug treatment revealed a recovery of estrous cycle in 60% of animals. GH treatment was also followed by an increased acquisition of shuttle-box active avoidance behavior and a facilitated retention of passive avoidance response. Compared to saline-injected controls, female rats treated with GH also exhibited a decrease of novelty-induced excessive grooming. The endocrine pattern of GH-treated aged female rats revealed a decrease in plasma prolactin levels and an increase in luteinizing hormone and 17 beta-estradiol levels as compared to those of control animals. These results support the concept that behavioral and endocrine alterations occurring in aging are not irreversible and that GH may interfere with these changes probably by means of its trophic action on different target organs.

Memory Deficits of Aged Male Rats Can Be Improved by Pyrimidine Nucleosides and n-Acetyl-Glutamine

The pyrimidine nucleosides uridine (URI) and cytidine (CYT), alone or associated with n-acetyl-glutamine (NAG), were injected acutely or subchronically to aged (26 months old) male rats of the Sprague-Dawley strain. Learning and memory abilities of the animals were studied with tests of avoidance behavior. The acquisition of active avoidance behavior was studied with the shuttle-box test. A step-through type of passive avoidance task was used to examine the retention of passive avoidance responses. The acquisition of the active avoidance behavior and the retention of the passive avoidance response were reduced in aged animals as compared with those of young animals. Neither the acute treatment of old rats with URI and CYT alone nor that associated with NAG exerted any effect on the behavioral tests. In contrast, the subchronic treatment with URI and CYT was followed by a facilitation of acquisition of active avoidance behavior in the shuttle box and of retention of passive avoidance responses in the dark box. A more potent effect on the acquisition of the shuttle-box behavior and on the retention of passive avoidance reaction was found in animals treated subchronically with the pyrimidine nucleosides associated with NAG. These effects may be related to the role of pyrimidines in the synthesis of ribonucleic acid, which is indispensable for learning and memory processes.

Dihydroergocristine and memory alterations of aged male rats

The ergot alkaloid derivative dihydroergocristine (DHECS) was injected acutely or subchronically to aged male rats of the Sprague-Dawley strain, 26 months old, at the dose of 0.05 or 0.1 mg/kg. Learning and memory ability of the animals were studied with tests of avoidance behavior. The acquisition of active avoidance behaviour was also studied. A step-throug type of passive avoidance task In the latt, the extinction of active avoidance behavior was also studied. A step-through type of passive avoidance task was used to examine the retention of passive avoidance responses. The acquisition of the active avoidance behavior and the retention of the passive avoidance response were reduced in aged animals as animals as compared to those of young animals. Acute treatment of old rats with DHECS was followed by a facilitation of acquisition of active avoidance behavior in the shuttle box and of retention of passive avoidance responses in the dark box. The effect on the acquisition and extinction of pole-jumping behavior after a single injection of DHECS at the beginning of the acquisition session was restricted tot he first acquisition trial. A more potent effect on the acquisition of the shuttle-box behavior and on the retention of passive avoidance reaction was found in animals treated subchronically with the ergot derivative (0.05 and 0.1 mg/kg for 10 days). These rats also showed a facilitation of acquisition and an inhibition of extinction of pole jumping behavior.

Enhancement by secoverine and physostigmine of retention of passive avoidance response in mice.

A one-trial passive avoidance test in the mouse, in which drugs were injected intraperitoneally immediately after the shocked acquisition trial, was used. The effects of enhancing central cholinergic transmission on retention of passive avoidance was investigated using secoverine, which blocks muscarinic autoreceptor-mediated inhibition of acetylcholine release, and using physostigmine, an acetylcholinesterase inhibitor. Secoverine (1.0-5.0 mg/kg) and physostigmine (0.1-0.4 mg/kg) were found to improve retention of the avoidance response measured 24 h after acquisition. These effects were augmented when the two drugs were given in combination. In contrast, atropine (5.0 mg/kg) tended to impair retention of passive avoidance and blocked the facilitatory effects of physostigmine. The results support the hypothesis of a novel approach to treatment of memory disorders based on blockade of muscarinic autoreceptors, to augment central cholinergic activity.

Age-dependent spontaneous EEG bursts in rats: Effects of brain phosphatidylserine

During aging, male Sprague-Dawley rats display increasing frequency of bursts of seizure-like EEG patterns. They also have a decreased retention of passive avoidance response and a loss of spontaneous alternation in a Y maze. A study was made on the effects of chronic administration of phosphatidylserine in aged rats. It was found that BC-PS reduced by 65% the number of seizures, and by 70% their duration. It also facilitated retention of passive avoidance and of spontaneous alternation behavior. These results suggest that phosphatidylserine can affect electrophysiological and behavioral parameters in aged rats probably by counteracting age-related biochemical changes.

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.

Sexual dimorphism in passive avoidance behavior of rats: Relation to body weight, age, shock intensity and retention interval

Female rats were inferior to age- and weight-matched males in the retention of a step-through type passive avoidance response 24 and 48 hr after the learning. This sex difference could be observed at different intensities of foot shock which was used as aversive stimulus during the single learning trial. Additionally, unlike in males, retention of the passive avoidance response in the females was not the function of shock intensity. Male and female rats, however, showed similar passive avoidance if tested immediately after the learning trial. The results suggest the existence of sexual dimorphism in memory processes.