Step-through Passive Avoidance Response Research Articles

Disruption of memory reconsolidation impairs storage of other, non-reactivated memory

Two hypotheses were tested in this study. First, blockade of neural activity by lidocaine immediately following the retrieval of a memory may impair the reconsolidation and subsequent expression of that memory. Second, a non-retrieved memory would not be affected by this lidocaine treatment. Since the basolateral nucleus of the amygdala (BLA) is involved in emotion-related memory, an intra-BLA lidocaine infusion was used immediately after the retrieval of two emotion-related memories, the step-through passive avoidance response (PA) and cocaine-induced conditioned place preference (CPP). Intra-BLA lidocaine infusion immediately after cocaine-induced CPP retrieval diminished CPP magnitude in retests. However, intra-BLA lidocaine infusion alone did not affect cocaine-induced CPP performance. Intra-BLA lidocaine infusion immediately after PA retrieval decreased PA performance in retests. Omission of PA retrieval procedure, intra-BLA lidocaine infusion did not affect subsequent PA performance. Surprisingly, intra-BLA lidocaine infusion immediately following the retrieval of PA or cocaine-induced CPP diminished both PA and cocaine-induced CPP performance in the retests. Finally, Fos-staining results revealed that a number of BLA neurons were activated by the retrieval of both cocaine-induced CPP and PA. We conclude that inactivation of neural activity in BLA immediately following retrieval of a fear or cocaine-conditioned memory can impair subsequent expression of both memories. More importantly, retrieval of a memory does not seem to be an absolute condition for rapidly changing the memory.

Quantitative trait loci for age-related memory dysfunction in SAMP8 and JF1 mice

The senescence-accelerated mouse (SAM) P8 strain exhibits severe age-related learning and memory deficits (LMD) well before the median age of survival. As a first step to clarify the genes involved in this deterioration, we have performed genetic analysis of SAMP8 using the whole genome scan for quantitative trait loci (QTLs) specifying the impairment in step-through passive avoidance response with F2 intercrosses of SAMP8 exhibiting short retention time (RT) and Japanese Fancy Mouse 1 (JF1) derived from Japanese wild mouse ( Mus musculus molossinus) exhibiting normal long retention time. Genetic markers were typed at 113 loci spanning all chromosomes except the Y. Five loci have been identified with significant linkage to chromosomes 1, 12, 13 and 15 by interval mapping of 264 F2 mice. Three of them on chromosomes 1, 12, and 13 are due to SAMP8 background, while two of them on chromosome 15 are derived from JF1 background despite parental JF1 strain shows normal phenotype.

Prenatal stress induces body weight deficit and behavioural alterations in rats: the effect of diazepam

Prenatal stress may induce intrauterine growth retardation, but it is not known whether a treatment with the anxiolytic benzodiazepine, diazepam may interfere with this phenomenon. A daily physical stress consisting of a forced immersion for 15 min in cold water was applied to pregnant rats of the Wistar strain from gestational day 5 until parturition. Animals were treated either with physiological saline or with diazepam (0.1 or 1 mg/kg/day) injected intraperitoneally 1 h prior to stress application. Control animals received injections of physiological saline but were not subjected to physical stress. Newborn pups subjected to prenatal stress showed reduced body weight as compared to control animals. Offspring were also examined for the appearance day of the following reflexes: cliff aversion, startle, righting, forelimb placing, forelimb grasping and bar holding. Hair growth, and first day of ears and eyes opening was also scored. At 60 days of age, male rats from the three experimental groups were subjected to behavioural tests, i.e., constrained swim (despair test) and step-through passive avoidance response. Animals subjected to prenatal stress showed a delayed appearance of all neonatal reflexes and behavioural deficits in adulthood, namely increased immobility in the despair test and reduced retention of a passive avoidance task. The prenatal treatment with diazepam totally counteracted the effect of stress, normalizing the time-course of neonatal reflexes and the behavioural responses in adulthood. No difference was seen between the effects of the two drug doses. It is concluded that prenatal physical stress may induce body growth retardation and may be considered as a model for human intrauterine growth retardation. The treatment with an anxiolytic benzodiazepine, such as diazepam, may counteract the effects of prenatal stress interfering with the biological consequences of stress concerning probably cerebral neurotransmitters in both the unborn foetus and the pregnant rat.

Effects of thioperamide, a histamine H 3 antagonist, on the step-through passive avoidance response and histidine decarboxylase activity in senescence-accelerated mice

The effect of thioperamide, a histamine H 3 receptor antagonist, on learning and memory was studied in the senescence-accelerated mice-prone strain (SAM-P/8) and normal-rate aging strain (SAM-R/1). In a passive avoidance test, SAM-P/8 mice of 12 months showed significant impairment of learning and memory compared with SAM-R/1 mice of the same age. Thioperamide significantly improved the response latency in SAM-P/8 mice when injected intraperitoneally at a dose of 15 mg/kg. The histidine decarboxylase (HDC) activity in the forebrain was significantly lower in SAM-P/8 mice than in SAM-R/1 mice. Thioperamide administration significantly potentiated HDC activity in the forebrain of SAM-P/8 mice as well as improving learning and memory. These results suggest that central histaminergic neurons may be involved in learning and memory impairment of SAM-P/8 mice, although other possibilities are not ruled out.

Diurnal variation in passive avoidance response and serum corticosterone in rats

A possible relationship between diurnal variation in performance of step-through passive avoidance response (PAR) and that in adrenocortical response was investigated. In Wistar-Imamichi strain rats, retention latency of PAR and serum corticosterone (CORT) level immediately after retention test were measured as a function of time of day. Basal CORT level was found to be low during early phase of light period, and thereafter to elevate toward dark period (Exp. 1). Eighty animals were divided into eight groups, which consisted of a combination of two diurnal times of training/testing (light phase = 14:00 and dark phase = 2:00) and four shock intensities for training (0, 0.5, 0.75, 1.0 mA) (Exp. 2). The latency of PAR was found to be longer in the light than in the dark phase, and CORT markedly increased only in the light phase in the groups with 0.75 mA. In addition, PAR was conducted at four times of day (8:00, 14:00, 20:00, 2:00) with 0.75 mA shock (Exp. 3). It was confirmed that the diurnal variation of PAR latency was associated with that the CORT elevation, with the maximum at 14:00 and the minimum at 2:00. These results indicate that diurnal variation in performance of PAR has a close relationship with that in emotional or stress response to aversive situation.

Learning behaviour in chronic vitamin E-deficient and-supplemented rats: radial arm maze learning and passive avoidance response

The effects of long-term vitamin E deficiency and supplementation on learning behaviour were investigated. Rats were fed vitamin E-deficient [VE(-)], -supplemented [VE(+)], or control standard food beginning after the age of 4 weeks. They were trained in an eight-arm radial maze learning task at the age of 17 months, and in a step-through passive avoidance response (PAR) task at the age of 25 months. In the radial maze task, both VE(-) and VE(+) animals required as many trials to reach the learning criterion as control animals. Scopolamine injection (0.25-0.5 mg/kg) after acquisition of the task decreased the number of correct choices dose-dependently; however, the degree of the drug effect on VE(-) and VE(+) rats did not differ from that on control rats. On the other hand, VE(-) animals showed significantly lower rate of avoidance response and VE(+) animals tended to show higher rate of avoidance response in the PAR task than did control animals. These results suggest that long-term vitamin E deficiency or supplementation does not influence general ability to acquire and maintain memory tasks in rats, but that it may affect learning behaviour, depending on the kind of task in which animals were trained.

Aspects op animal experiments for evaluation of cognitive enhancers: In particular, the behavioral characteristics of mongolian gerbils

1.1. The step-through passive avoidance response and discrete lever-press avoidance response of Mongolian gerbils were evaluated to point out the basic problems in the learning and memory tests in this species.2.2. Mongolian gerbils exhibited extremely poor acquisition and maintenance of the passive avoidance response.3.3. In contrast to the result under the passive avoidance situation, Mongolian gerbils demonstrated an excellent performance under the discrete lever-press avoidance situation.4.4. A 5-min brain ischemia elicited a severe morphological damage of the pyramidal cells in hlppocampal CA1 region.5.5. A small part of such ischemia animals showed a deficit of acquisition of the discrete lever-press avoidance.6.6. These results suggest that there is merit and demerit of the acquisiton dependent on the type of tasks, and that the brain function of Mongolian gerbils may be maintained even after the ischemic operation.

マウスにおけるＦｅｂａｒｂａｍａｔｅ（ＭＳ‐５４３）の行動薬理作用 移所運動，能動的回避反応および受動的回避反応による評価

Febarbamate (MS-543: 100 and 10000 mg/kg, p.o.) neither produced significant change in the mouse's ambulatory activity after the single administration nor modified the ambulation-increasing effects of the following drugs: methamphetamine (2 mg/kg, s.c.), apomorphine (0.5 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). MS-543 (100 and 1000 mg/kg, p.o.) scarcely affected the established active avoidance response in mice under a discrete shuttle avoidance situation. However, MS-543 (1000 mg/kg, p.o.) tended to enhance the decrease in response and/or avoidance rates induced by chlorpromazine (2 mg/kg, s.c.) and physostigmine (0.2 mg/kg, s.c.). Finally, the disruption of the step-through passive avoidance response induced by pre-training administration of scopolamine (0.5 mg/kg, s.c.) in a one trial task was reduced when MS-543 was administered before the scopolamine administration. However, the post-training administration of MS-543 was without effect on the scopolamine-induced disruption of the avoidance. Furthermore, no significant effect of MS-543 was observed in the multi-trial passive avoidance task. The present results suggest that MS-543 activates cholinergic function and possesses a slight sedative action.

3-((±)-2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CCP) and phencyclidine produce a deficit of passive avoidance retention in rats

3-((±)-2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CCP), phencyclidine (PCP) and diazepam were evaluated for their ability to produce a deficit for a single trial step-through passive avoidance response in rats. Pretraining administration with CCP at doses ranging from 2.0 to 10.0 mg/kg s.c. significantly decreased retention latencies 24 h after passive avoidance training. Similar effects were found with PCP at doses ranging from 0.5 to 1.7 mg/kg s.c. and diazepam at doses between 5.0–18.0 mg/kg s.c. Pretraining administration with the benzodiazepine antagonist, RO15-1788 at doses between 0.1–15 mg/kg s.c., did not alter retention latencies. Co-administration of RO15-1788 (0.01–15.0 mg/kg s.c.) with CCP (6.0 mg/kg s.c.) or PCP (1.0 mg/kg s.c.) failed to block decreases in latencies. However, when RO15-1788 was co-administered with diazepam (9.0 mg/kg s.c.) a dose-related antagonism of diazepam's effects were found. These results suggest that the behavioral actions of CCP and PCP on passive avoidance retention are not mediated via the benzodiazepine receptor complex.

ラットの実験的健忘モデルにおけるＮａｆｔｉｄｒｏｆｕｒｙｌ ｏｘａｌａｔｅ（ＬＳ‐１２１）の作用

Effects of naftidrofuryl oxalate (LS-121) on experimental amnesia models, which were induced by cycloheximide (CXM), scopolamine (SCOP) and basal-forebrain (BF) lesion, were investigated using the step-through passive avoidance response in rats. In the retention test, a cut-off time of 600 sec was employed for the measurement of step-through latency (STL). The animals, that showed over 300 sec of STL was regarded as having the criterion of memory retention (% of retention). Increase in both parameters of STL and % of retention was regarded to indicate that the drug was able to improve the amnesia. If only one of the two parameters was increased, we considered that the drug had a tendency to improve the amnesia. Pretraining, post-training and pre-retention treatment of LS-121 (25 mg/kg) improved CXM- and SCOP-induced amnesia. Post-training treatment of LS-121 (25 mg/kg) showed a tendency to improve the BF lesion-induced amnesia. These results suggest that the antiamnesic action of LS-121 may be produced through an activation of the acetylcholinergic neuronal system. Since it improved the amnesia when administered in the pre-retention test, there is a possibility that LS-121 has not only a protective effect, but also a therapeutic effect. Furthermore, it is suggested that LS-121 may also have a therapeutic effect on Alzheimer's disease, since it showed a tendency to improve the BF lesion-induced amnesia.

The effects of lindane, DDT, and chlordecone on avoidance responding and seizure activity

Male adult Fischer-344 rats were given various doses of lindane (0, 15, and 30 mg/kg, po), chlordecone (0, 25, 50, or 100 mg/kg, ip), or p,p′-dichlorodiphenyltrichloroethane ( p,p′-DDT) (0, 25, 50, or 100 mg/kg, po) and tested for their ability to perform a two-way shuttle box task or to learn and retain a step-through passive avoidance response. Administration of p,p′-DDT or chlordecone 3 hr prior to acquisition did not affect the number of shuttle box avoidance responses made during a 60-trial training task, while responses during the intertrial interval (ITI) were decreased. Rats receiving 15 or 30 mg/kg of lindane made fewer avoidance responses, but did not differ from controls in terms of the number of responses during the ITI. When 30 mg/kg lindane was given 3 hr prior to passive avoidance acquisition, retention was impaired 7 days later; the lower dose of lindane, and all doses of chlordecone or p,p′-DDT had no effect under these conditions. When these chemicals were given immediately after passive avoidance training, animals treated with lindane were not affected. Animals receiving 100 mg/kg of p,p′-DDT or chlordecone displayed marked signs of toxicity and animals tested 7 days after training showed an impaired retention. Pretreatment with anticonvulsants such as phenobarbital and chlordiazepoxide, which may enhance GABA-mediated responses, blocked the disruptive effecs of lindane (30 mg/kg) on shuttle box avoidance. The seizure-related activity produced by a higher dose of lindane (60 mg/kg) and kainic acid, a hippocampal excitotoxin, was also blocked by phenobarbital and chlordiazepoxide. Pretreatment with phenytoin, which is thought to bind to the inactivation gates of sodium, had no effect on the effects produced by lindane or kainic acid. These data suggest that treatment with nonconvulsant doses of lindane can interfere with the ability to acquire and use new information and that these effects may be associated with alterations in GABA.

Vinpocetine enhances retrieval of a step-through passive avoidance response in rats

Vinpocetine, vincamine, apovincaminic acid, vinconate, aniracetam, Hydergine ®, and pemoline were evaluated for their ability to enhance retrieval of a step-through passive avoidance response in rats. The percentage of rats performing the avoidance response was found to decrease as a function of the number of days between training and retention testing (Day 1, 100%; Day 2, 65%; Day 3, 23%; Days 4 and 5, 0%). Vinpocetine administered 60 minutes prior to testing for retention significantly increased the number of rats performing the passive avoidance response. Retrieval enhancement was dose-related in an inverted U-shaped function with the effective doses at 18 and 30 mg/kg PO. In contrast, apovincaminic acid (1–400 mg/kg PO), vincamine (1–200 mg/kg PO), vinconate (1–200 mg/kg PO), aniracetam (1–300 mg/kg PO), Hydergine ® (0.1–10mg/kg PO), and pemoline (1–30 mg/kg PO) were not effective. These data support the view that vinpocetine has cognition-activating abilities as defined in an animal model of memory retrieval.

Vinpocetine: Nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats

Vinpocetine, vincamine, aniracetam, and Hydergine®, compounds with purported cognition activating activity, were evaluated for their ability to prevent scopolamine-induced and hypoxia-induced impairment of passive avoidance retention (24 hr) in rats. Vinpocetine (peak effect dose [PED]=200 mg/kg PO), aniracetam (PED=100 mg/kg PO), vincamine (PED=30 mg/kg PO), and Hydergine® (PED=1 mg/kg PO) prevented memory disruption by scopolamine. Vinpocetine (PED=3 mg/kg PO) and aniracetam (PED=30 mg/kg PO) were also effective in preventing disruption of passive avoidance retention impaired by 7% oxygen hypoxia. In contrast, Hydergine® (0.05 to 3 mg/kg PO) and vincamine (0.3 to 100 mg/kg PO) were not effective against hypoxia-induced impairment. Hydergine® at doses > 10 mg/kg PO markedly impaired motor function. In both tests the protection was dose-related for all test substances in an inverted U-shaped manner. Mecamylamine (1, 3, 10 mg/kg SC), (−)-nicotine (0.1 to 0.4 mg/kg SC), apovincaminic acid (1–400 mg/kg PO) and pemoline (1–100 mg/kg PO) did not protect against memory impairment induced by either procedure. These data support the view that vinpocetine, a compound chemically distinct from the pyrrolidinones, has a cognitive activating ability as defined in models of both scopolamine-induced and hypoxia-induced memory impairment in rats.

P-Chlorophenylalanine-produced effects on behavior in intact and brain-damaged rats

Introduction: Our aim was to determine if a reduction of serotonin (5-HT) synthesis in the brain would provide any protection from the behavioral alterations induced by hippocampal brain-damage. The development of open-field activity (5 minute sessions) over two weeks and the acquisition of a passive avoidance task were chosen for study. Methods: There were 3 groups of lesioned rats - those hippocampal aspiration lesions, those with only damage to the neocortex overlying the hippocampus, and a sham-operated group. Half of each group was treated 300 mg/kg p-chlorphenylalanine (PCPA) for 3 successive days to deplete levels of 5-HT and the other half were given the saline vehicle alone. [Hippocampal damage is associated with increased activity in the open field and impaired learning of the step-through passive avoidance response.] Results: 1/ Animals with hippocampal damage became hyperactive in the second week after operation. 2/ PCPA treatment had no effect on locomotion, (nor on the frequently observed thigmotaxic nature of the behavior) 3/ Rearing was initially depressed after the operation, and PCPA treatment facilitated its recovery - but PCPA decreased rearing in intact animals during the second week of testing. 4/ Reduced levels of grooming were seen in hippocampal animals, while PCPA reduced grooming in those with neocortical damage 5/ The animals with hippocampal damage were impaired in witholding response in the passive avoidance task - those treated with PCPA performed even worse in not witholding the shock-reinforced step-through response. This contrasted with the intact animals, where PCPA treatment reduced the amount of footshock the animals were exposed to in the task Conclusions: .The results are consistent with a role for mesolimbic 5-HT innervation of the dorsal hippocampus having an influence on novelty-elicited responses (e.g. grooming in home vs. novel cage and investigative rearing behavior) and in modulation of the sensitivity of response to electric footshock (hypersensitive in PCPA-intact animals, hyposensitive in PCPA-hippocampal animals).

Anti-amnesic effect of ACTH 4–10: Its independence of the nature of the amnesic agent and the behavioral test

It was found previously that ACTH 4–10 is able to alleviate the CO 2-induced retrograde amnesia for a step-through passive avoidance response when injected into rats 1 hr prior to the retrieval test. The present investigation was undertaken to establish whether ACTH 4–10 has a similar effect if a different amnesia agent and a different behavioral task are used. It appeared that electroconvulsive shock induced amnesia for a one-trial thirst-motivated response. This amnesia could be reduced by administration of ACTH 4–10 1 hr prior to the retrieval test. Administration of ACTH 4–10 1 hr prior to the acquisition was ineffective. It was concluded that ACTH 4–10 exerts a retrieval-promoting effect independent of the nature of the amnesic agent and the behavioral task.

The effects of ACTH- and vasopressin-analogues on CO 2-induced retrograde amnesia in rats

Amnesia for a one-trial step-through passive avoidance response was induced in rats by application of CO 2 until respiratory arrest occurred. The ACTH-analogue ACTH 4–10 alleviated the amnesia when administered 1 hr prior to the retrieval test but not when given 1 hr prior to the acquisition trial. The behaviourally inert ACTH-analogue ACTH 11–24 appeared to have no effect on the amnesia. The vasopressin-analogue desglycinamide lysine vasopressin (DG-LVP) antagonized the amnesia when administered 1 hr prior to the acquisition trial or 1 hr prior to the test trial. The relevance of these date to present theories on amnesia is discussed.