Effect of exposure to stress applied during early ontogenesis on the avoidance reaction in young rats

A study was made of the influence of stress (swinging) applied on the first to the fifth day of life of newborn rats, on acquistion of active unilateral avoidance, passive avoidance of a dark "dangerous" compartment, the relative weight of the brain and absolute increase in the weight of the body at an early age. It was shown that in four-week old rats the stress significantly worsens active avoidance acquisition. In two-month old animals avoidance of a dark "dangerous" compartment, i.e. "passive" avoidance, tested immediately after application of electric current is more pronounced in stressed rats. No difference was found in the relative weight of the brain and the absolute increase in the weight of the body between control and stress groups of the animals.     

The socially enriched environment in early age alters the exploratory activity and ability for learning in rats

The effects of socially enriched environment on exploration activity in early age and avoidance learning in adult rats were studied. Rats reared in enriched environment were housed with mother and three young rats before weaning. Control rats were housed with mother only. An increase in exporation activity in the open-field test and modified plus-maze was observed in the socially reared rats. The capability for two-way avoidance conditioning was significantly improved in adult socially reared rats.     

Influence of acoustic signal with ultrasonic components on the development of defensive conditioned reflex in Wistar rats

Short-term (90 s) effects of the complex acoustic signal (CAS) with ultrasonic components on the development of defensive conditioned reflex of two-way active avoidance in a shuttle-box were studied in female Wistar rats. The learning ability of rats was measured on a scale designed in our laboratory. It was shown that CAS stimulation triggered an audiogenic seizure of different strength in 59% of animals. The CAS was extremely stressful for Wistar rats: it prevented the active avoidance learning in early terms after its application (the first training session in 4 or 6 days). This effect did not depend on the presence or intensity of audiogenic seizures during CAS. In the second training session in 9 days (the first session was in 4 days), learning was impaired as compared to control without CAS. However, during repeated training procedure 1.5 months after the CAS (the first session in 6 days), rats rapidly reached the criterion of learning (10 consecutive avoidance reactions). On the other hand, if the CAS was presented with different time lags (immediately, in 3 or in 45 days) after the first training session, the ability of animals to learn during the second session was not impaired both in early and late terms after exposure to the stressor. The results suggest that exposure to CAS prevents development of short-term memory but does not affect consolidation process and long-term memory.     

Prefrontal cortex aspiration in pups and juvenile rats: behavioural changes and recovery of function

Male Wistar rats sustaining prefrontal cortex aspiration or sham operation at 6 days or 30 days of age were submitted to the following behavioural tests: open-field, acquisition and retention of two-way active as well as passive avoidance tasks. In the open-field the locomotor activity proved enhanced in all the aspirated animals and this enhancement lasted for 30 days. In the two-day active avoidance task, an acquisition deficit was observed in both aspirated groups; but when retrained one month later, they were able to acquire the avoidance task like sham-operated rats and no difference appeared between the groups aspirated at 6 or at 30 days of age. Concerning the passive avoidance task, no difference could be detected between aspirated and sham-operated animals of both groups except that the rats aspirated at an early age (6 days) seemed to display a better avoidance ability in the retention test. These behavioural alterations (hyperactivity and impairment of the acquisition of the 2-way active avoidance) resulted from the prefrontal cortex aspiration, at whatever age this aspiration was performed (6 days or 30 days). They disappeared after a postoperative recovery period of about one month, as evidenced by this longitudinal study.     

The effect of administering corticoliberin into the striatum on the open-field and shuttle-box behaviors of KHA and KLA strain rats]

The effects of corticotropin-releasing hormone (CRH) injected into the dorsal neostriatum on the open-field and shuttle-box behavior were studied in rats with high (Koltushi high avoidance, KHA) and low (Koltushi low avoidance, KLA) capability for avoidance learning. The effects of this hormone on the behavior of these rat strains were different. In KLA rats with passive strategy of behavior the CRH injection led to a rapid locomotor activation in the open field, while the rats with active behavioral strategy (KHA) reacted to the injection by a significant decrease in locomotion and change for the passive mode of behavior. The same CRH effects on locomotion were obtained in the shuttle-box experiments. Moreover, in the KLA rats the neurohormone injection resulted in an improvement of avoidance learning in contrast to the KHA rats, in which CRH substantially impaired avoidance learning. The obtained evidence is discussed in terms of the important role of striatal CRH in the choice of behavioral strategy in stress.     

Passive avoidance deficits following lesions of the posteroventral hippocampo-subiculo-entorhinal area in the developing rat

Young rats, 13, 16, and 20 days of age, underwent discrete bilateral electrolytic lesions of the posteroventral hippocampo-subiculo-entorhinal area, and were trained on a cool-draft-stimulus passive avoidance task 20 min later. Significant deficits in passive avoidance learning were observed at all ages studied following either small or more extended damage as compared to performance of sham-lesioned animals. The impairment was dependent upon the size of the lesion. Extended bilateral lesions of the parietal cortex overlying hippocampus induced no deficit. These results confirm that this part of the hippocampal complex plays a role in passive avoidance learning in the rat. They also show that this control of behavior is already established by the second week of life, thus supporting our previous experiments that demonstrate a cholinergic nicotinic involvement of this region in acquisition of passive avoidance as early as the 11th day of age.     

Analysis of the process of learning in the formation of the conditioned reflex of avoidance in rats

During acquisition of avoidance conditioned reflex (CR) in shuttle box by electric shock it is shown that the performance of that defence reaction is induced by the joint action of two factors: general arousal of animals and motivation. Motor activity of rats in an "open field", the number of short-latency (2s) and intersignal responses during formation of the avoidance CR are in index of the general arousal of rats. An artificial increase in the general arousal of animals by caffeine induces acceleration of CR performance. A constant level of the general arousal of rats is one of the reasons that oxytocin does not influence the rate and dynamics of the avoidance CR performance in rats.     

Evoked potential correlates of early conditioning in the rat ontogeny.

In rats aged 2-8 weeks cortical EP to CS (20 flash - tone combinations, 0,9/sec, reinforced since the 10th application by electric shocks to the hind leg) were studied within different kinds of behavioral responses during avoidance learning and extinguishing. In contrast to our results in freely moving rats no developmental trend was found in this kind of avoidance (lifting of the hind leg). Average EP within reinforced trials (with escape or no reactions) differed in isolated application of CS from those when both CS and US were acting together. In younger animals the EP to CS combined with US were characterized by an evident late negative wave which shifted later (5-6 weeks toward the early negative complex. The EP changes in the auditory cortex were more pronounced, whereas visual EP with CS-US combination were rather decreased. In the youngest animals (2 weeks) the auditory EP within trials with avoidance were characterized by a distinct short latency deflection of the first positive wave, whereas in EP to extinguished CS the second deflection of the first positive wave prevailed. Also in these phenomena, the typical changes were clearly revealed in the auditory cortex. At later developmental stages (starting the 3rd, more prominently the 4th and 5th week) the wave following primary positive - negative complex was shifted toward the negativity if the animal responded by an avoidance; on the contrary an ample positive, often a double-peak wave arose if the response was extinguished. The stimulus and reaction dependence in the cortical EP showed the role of not yet fully mature cerebral cortex in avoidance learning. Both, fast as well as with some delay running processes participated in the observed phenomena during the ontogenetical development.     

Study on the optimum number of trials and intensity of unconditioned stimulants and strain difference in the two-way shuttle-box avoidance test using rats

In order to determine the optimun conditions suitable for a number of trials and the intensity of unconditioned stimulant (US) in the two-way shuttle-box avoidance test in Sprague-Dawley strain rats, which are used most frequently in reproduction studies, conditioned avoidance response was observed under various conditions for 30 and 60 trials and the low and high US levels. Investigation was also conducted in Wistar rats under a high US level with 30 and 60 trials. Latency time of the escape response in Sprague-Dawley rats was shortened with increasing trials. Body weight gains of both strains of rats in the high US level with the 60-trial group decreased during the observation period. These findings suggest that the high US level with the 60-trial group is not suitable for the two-way shuttle-box avoidance test. The rate and latency time of the avoidance response were lower in Wistar rats than in Sprague-Dawley rats, although those of the escape response were higher. Significant changes in the following were observed, mainly from first to third sessions: the avoidance rate of all groups in strains of rats, escape rate of 60-trial group in Sprague-Dawley rats, avoidance and escape latency time of the 60-trial groups in both strains of rats and escape latency time of the 30-trial group in Sprague-Dawley strain rats.     

Chronic early leucine administration induces behavioral deficits in rats.

Sustained levels of leucine comparable to those of human Maple Syrup Urine Disease (MSUD) were achieved in blood and brain of rats by subcutaneous leucine administration twice a day from the 6th to the 28th day of life. Control rats were treated with saline in the same volumes. Behavioral studies using aversive and nonaversive tasks were performed during adult age. Chronic early leucine treatment impaired acquisition of a two-way shuttle avoidance task and altered habituation to an open field. Our results suggest that early postnatal leucine administration induces long-lasting behavioral deficits.     

新生期触觉刺激和母婴分离对雌性大鼠成年后的焦虑和情绪记忆的影响

采用split-litter法对仔鼠进行分组和处理,共5组NTS组(未经实验人员抓握和标记),PND2—9TS组和PND10—17TS组(分别在仔鼠出生后的2—9天、10—17天,每天短暂抓握和标记仔鼠),PND2—9MS组和PND10—17MS组(分别在仔鼠出生后的2—9天、10—17天,除了按TS组相同方式抓握并在不同部位标记外,每天把仔鼠与母鼠分离1h)。待雌鼠成年后,进行明/暗箱测试和一次性被动回避反应测试。结果发现与NTS组相比,PND2—9TS组和PND10—17TS组的雌鼠在明/暗箱测试中停留于明室的累计时间明显较长,在被动回避作业中的重测试潜伏期也明显较长,表明新生期的触觉刺激经历减少雌性大鼠成年后在新异环境中的焦虑,并改善情绪记忆。与相应TS组相比,MS处理组的所有行为指标都无显著性差异,说明短时间母婴分离对雌鼠成年后的焦虑和情绪记忆无明显影响。结果提示,新生期的触觉刺激和母婴分离经历对仔鼠神经系统的发育产生不同的长期效应。     

Effect of dalargin on the behavior of rats subjected to intrauterine ethanol exposure

Influence was studied of dalargin--synthetic analogue of enkephalin administered in early postnatal period to young rats with intrauterine ethanol injection, on their behaviour and conditioned activity. Parameters were established of spontaneous motor activity, behaviour in the open field, acquisition and preservation of conditioned reflexes of passive and active avoidance in experimental and intact rats, injected with dalargin. A reduction of sensitivity to corasol convulsive effect was observed under the influence of dalargin.     

Social Transmission of Avoidance Behavior under Situational Change in Learned and Unlearned Rats

Background

Rats receive information from other conspecifics by observation or other types of social interaction. Such social interaction may contribute to the effective adaptation to changes of environment such as situational switching. Learning to avoid dangerous places or objects rapidly occurs with even a single conditioning session, and the conditioned memory tends to be sustained over long periods. The avoidance is important for adaptation, but the details of the conditions under which the social transmission of avoidance is formed are unknown. We demonstrate that the previous experience of avoidance learning is important for the formation of behaviors for social transmission of avoidance and that the experienced rats adapt to a change of situation determined by the presence or absence of aversive stimuli. We systematically investigated social influence on avoidance behavior using a passive avoidance test in a light/dark two-compartment apparatus.

Methodology/Principal Findings

Rats were divided into two groups, one receiving foot shocks and another with no aversive experience in a dark compartment. Experienced and inexperienced rats were further divided into subjects and partners. In Experiment 1, each subject experienced (1) interaction with an experienced partner, (2) interaction with an inexperienced partner, or (3) no interaction. In Experiment 2, each subject experienced interaction with a partner that received a shock. The entering latency to a light compartment was measured. The avoidance behavior of experienced rats was inhibited by interaction with inexperienced or experienced partners in a safely-changed situation. The avoidance of experienced rats was reinstated in a dangerously-changed situation by interaction with shocked rats. In contrast, the inexperienced rats were not affected by any social circumstances.

Conclusions/Significance

These results suggest that transmitted information among rats can be updated under a situational change and that the previous experience is crucial for social enhancement and inhibition of avoidance behavior in rats.     

Effect of alpha-tryptophan on conditioning and behavior in rats with experimental pathology of the thyroid gland

Effects of L-tryptophan on learning and behavior were studied in male rats with a deficit or excess of thyroid hormones. Learning was assessed in active avoidance paradigm, and behavior was estimated in the "open-field" test. It was found that L-tryptophan restored the capability of thyreoidectomized rats for acquisition and reproduction of the active avoidance reaction and increased the exploratory behavior of these rats in the open-field. In triiodothyronine treated rats, L-tryptophan eliminated a light stimulatory effects of thyroid hormones on the processes of formations and retention of the active avoidance reaction, increased the exploratory activity, but decreased grooming in the open-field.     

Total body 4.5 Gy gamma irradiation-induced early delayed learning and memory dysfunction in the rat.

In an attempt to determine the consequences of total body radiation damage on learning and memory in the rat, twenty-eight male Wistar rats aged 4 months received 4.5 Gy total body gamma-irradiation (TBI) while 28 rats received sham irradiation. Sequential behavioral studies of negative reinforcement including a/ one- and b/ two-way avoidance tasks were undertaken. a/ One-way avoidance test: this test was performed before and after TBI. Prior to irradiation both groups were similar. At 20 days (D) and at 3 months post-TBI, irradiated rats had a significantly lower percentage of avoidance than controls but no statistical difference was found at 5 months post-TBI. b/ Two-way avoidance test: this test was performed only after TBI. At days 21, 22, 23, 24, (leaming) and at 4 or 6 months (recalls) post-TBI the mean percentage of avoidance was significantly lower in irradiated than in control rats. This study demonstrates that total-body exposure to 4.5 Gy gamma-irradiation induces behavioral dysfunction affecting learning and transitorily memory. These results suggest that a relatively low dose of total body irradiation can induce neurological complications, which persist 4-6 months later.     

Dietary n-3 polyunsaturated fatty acid deprivation together with early maternal separation increases anxiety and vulnerability to stress in adult rats

Low concentrations of n-3 polyunsaturated fatty acid (PUFA) and chronic stress are implicated in susceptibility to mood disorders. We have investigated the combined effects of chronic n-3 PUFA dietary deficiency and early maternal separation (MS) stress on the reactivity to stressful situations of rats as adults. Pups fed a control or an n-3 PUFA deficient diet were daily separated for two weeks before weaning They were all tested at 3 month-old to determine their anxiety, and their ability to learn two aversive tasks differing in the control they could exert on the situation: auditory fear conditioning and brightness avoidance discrimination. Neither the n-3 PUFA-deficient diet nor MS alone significantly affected behavior. But n-3 PUFA-deficient rats that had been separated were more anxious and fearful in inescapable situations, while their ability to cope with an aversive avoidance task remained unaffected. These results support the notion that PUFA-unbalanced diet, together with stress, may be a determinant risk factor in emotional disorders.     

Effect of conditioned-reflex bilateral avoidance learning on lipid components of the rat brain

The active avoidance training of rats resulted in a depletion of lipid peroxidation (LPO) products in cerebral cortex. LPO inhibition was also shown in cerebral cortex of "active control" group receiving +non-combined stimuli (the effect of short-term stress). LPO inhibition was more pronounced in rats staining a training criterion compared to rats which received combined stimuli but did not reach the criterion. In the active control group LPO inhibition was accompanied by total phospholipids accumulation and cholesterol depletion in cortical lipid extracts. Irrespective of attaining the criterion in all rats trained for active avoidance the accumulation of cholesterol was seen. Active avoidance training affected also the phospholipid composition of cerebral cortex.     

Functional role of the dorsal and ventral hippocampus in defensive behavior in the rat

Bilateral electrolytic lesions of the dorsal hippocampus of white rats were shown to facilitate elaboration of a conditioned response of active avoidance of pain shock in a shuttle-box. The lesions of the ventral hippocampus had no effect on conditioning. The ventral hippocampal lesions led to a complete failure to form differential inhibition. In rats with the dorsal hippocampal lesions an acquisition of partial (up to 60 per cent) discrimination of stimuli was possible. The differences in avoidance conditioning and elaboration of differential inhibition in rats with the dorsal and ventral hippocampal lesions are supposed to be caused by the changes of general excitability and emotional state of animals as well as by a specific role of the ventral hippocampus in memory consolidation.     

D-Pen2-[D-Pen5]enkephalin impairs acquisition and enhances retention of a one-way active avoidance response in rats.

We reported previously that D-Pen2-[D-Pen5]enkephalin (DPDE), a delta-opioid receptor selective analog of Leu-enkephalin, impairs acquisition of an automated jump-up avoidance response in rats and acquisition of a one-way active avoidance response in mice. In the present study we investigated the effects of DPDPE on one-way avoidance conditioning in rats. The rats received two escape-only trials on day 1 and eight additional training trials on day 2. DPDPE (1.16 micrograms/kg IP) administered prior to training on day 2 impaired acquisition of the avoidance response. On the other hand, DPDPE (0.332 microgram/kg IP) administered following presentation of the two escape-only trials on day 1 significantly enhanced retention, as measured by improved one-way active avoidance performance on day 2. These results indicate that activation of delta-opioid receptors by DPDPE has a modulatory effect on acquisition and retention of aversively motivated performance.     

Rapid and Transient Learning-Associated Increase in NMDA NR1 Subunit in the Rat Hippocampus

Several lines of evidence indicate that glutamate NMDA receptors are critically involved in long-term potentiation (LTP) and in certain forms of learning. It was previously demonstrated that memory formation of an inhibitory avoidance task in chick is specifically associated with an increase in the density of NMDA receptor in selected brain regions. Here we report on the effect of a one trial inhibitory avoidance training in rats, a hippocampal-dependent learning task, on the levels of different subunits of the glutamate NMDA receptor in synaptic plasma membranes (SPM) isolated from the hippocampus. Training rats on a one trial inhibitory avoidance task results in a rapid, transient and selective increase (+33 %, p < 0.05) in NMDA NR1 subunit expression in hippocampal SPM of rats sacrificed 30 min posttraining. No changes were observed at 0 or 120 min after training or in shocked animals in comparison to naive control rats. In addition, no training-associated increase in the levels of NMDA NR2A and NR2B or AMPA GluR 2/3 subunits was observed at any timepoint tested. In conclusion, the present findings support the hypothesis that alterations in expression of synaptic NMDA NR1 subunits in the hippocampus are specifically associated with memory formation of an inhibitory avoidance task and strongly suggest that hippocampal NMDA receptors are crucially involved in the neural mechanisms underlying certain forms of learning.These authors contributed equally to this work