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Spared retention of inhibitory avoidance learning after posttraining amygdala lesions.

Previous findings indicate that the memory-impairing effects of posttraining amygdala lesions are attenuated by increasing the number of training trials given prior to the induction of the lesion. The aim of this experiment was to determine whether the degree of impairment is also influenced by the footshock intensity used during training. Rats were given 1 trial of inhibitory avoidance (IA) training with either no footshock or a footshock at 1 of 3 intensities. Sham or neurotoxic amygdala lesions were induced 1 week later. On a retention test performed 4 days after surgery, the performance of all amygdala-lesioned rats given footshock training, including those given the lowest training footshock, was better than that of amygdala-lesioned rats given no training footshock. These findings of preserved retention of IA learning in rats given posttraining amygdala lesions do not support a general hypothesis that the amygdala is a locus of permanent changes underlying aversively motivated learning.

Amygdala↗

Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe.

2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn-VPA (16-85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl-4-yn-VPA also influenced memory consolidation processes as, when given at 3 h post-passive avoidance training, the amnesia induced by scopolamine given 6 h post-training was prevented in a dose-dependent manner. Chronic administration of pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition-enhancing qualities of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.

Aging↗

Mild hypoxia preconditioning prevents impairment of passive avoidance learning and suppression of brain NGFI-A expression induced by severe hypoxia.

The aim of this work was to study effects of mild preconditioning hypobaric hypoxia (380 Torr for 2 h, repeated 3 or 6 times spaced at 24 h) on brain NGFI-A immunoreactivity and passive avoidance (PA) behavior in rats exposed to severe hypoxia (160 Torr for 3 h). Severe hypobaric hypoxia produced extensive neuronal loss in hippocampal CA1, while the preceding hypoxic preconditioning had clear protective effect on neuronal viability of vulnerable hippocampal cells. Besides, the hypoxic preconditioning prevented impairment of acquisition and retention of PA caused by severe hypoxia. The six-trial hypobaric preconditioning was more effective in protection against PA learning deficits in severe hypoxia exposed rats than the three-trial preconditioning. The preconditioning up-regulated severe hypoxia-suppressed neocortical and hippocampal expression of NGFI-A, suggesting a possible role for NGFI-A in the neuroprotective mechanisms activated by hypoxic preconditioning.

Analysis of Variance↗

The action of isatin (2,3-dioxoindole) an endogenous indole on brain natriuretic and C-type natriuretic peptide-induced facilitation of memory consolidation in passive-avoidance learning in rats.

Isatin is an endogenous indole which has been shown to counteract some of the effects of atrial natriuretic peptide (ANP) both in vitro and in vivo. The present study was designed to determine whether it could antagonise in vivo effects of the related peptides brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). The model used was consolidation of memory in a one-trial step-through passive-avoidance paradigm in the rat. Previous studies have shown that all three peptides (1 microg intracerebroventricular) can consolidate such learning and increase latency to entry a dark box. Isatin was given intraperitoneally at doses of 5, 10 and 50 mg/kg before the peptide, or a saline control. Both BNP and CNP significantly increased the latency of entry. Isatin alone had no effect. Isatin reduced the effect of both BNP and CNP; this was significant for its effect on BNP at 50 mg/kg and on CNP at both 10 and 50 mg/kg. These results show that isatin can inhibit behavioural effects of BNP and CNP as well as ANP.

Animals↗

Chronic amphetamine exposure during the preweanling period does not affect avoidance learning or novelty-seeking of adult rats.

The purpose of the present study was to determine whether exposure to amphetamine during the preweanling period would impact the learning or reward processes of rats tested in adulthood. In three experiments we examined whether amphetamine treatment (0-10 mg/kg per day) on postnatal days 11-17 altered the subsequent performance of adult Sprague-Dawley rats on a step-down passive avoidance, active avoidance, or novelty-seeking task. There was no evidence that postnatal amphetamine exposure affected performance on any of these tasks. These results suggest that the long-term impact of pre- and postnatal psychostimulant exposure differs, because in utero stimulant treatment is known to produce learning deficits and decrease reinforcement efficacy of rats tested in adulthood.

Adrenergic Agents↗

A synthetic peptide ligand of neural cell adhesion molecule (NCAM) IgI domain prevents NCAM internalization and disrupts passive avoidance learning.

The neural cell adhesion molecule (NCAM) mediates cell adhesion and signal transduction through trans-homophilic- and/or cis-heterophilic-binding mechanisms. Intraventricular infusions of anti-NCAM have revealed a functional requirement of NCAM for the consolidation of memory in rats and chicks in a specific interval 6-8 h after training. We have now extended these studies to a synthetic peptide ligand of NCAM (C3) with an affinity for the IgI domain and the capability of inhibiting NCAM-mediated neurite outgrowth in vitro. Intraventricular administration of a single 5 microg bolus of C3 strongly inhibited recall of a passive avoidance response in adult rats, when given during training or in the 6-8-h posttraining period. The effect of C3 on memory consolidation was similar to that obtained with anti-NCAM as the amnesia was not observed until the 48-h recall time. The unique amnesic action of C3 during training could be related to disrupted NCAM internalization following training. In the 3-4-h posttraining period NCAM 180, the synapse-associated isoform, was down-regulated in the hippocampal dentate gyrus. This effect was mediated by ubiquitination and was prevented by C3 administration during training. These findings indicate NCAM to be involved in both the acquisition and consolidation of a passive avoidance response in the rat. Moreover, the study provides the first in vivo evidence for NCAM internalization in learning and identifies a synthetic NCAM ligand capable of modulating memory processes in vivo.

Animals↗

Effects of intrahippocampal injections of the cholinergic neurotoxin AF64A on open-field activity and avoidance learning in the rat.

The effects of direct intrahippocampal administration of the cholinergic neurotoxin, AF64A, were investigated in male rats. Bilateral injections of AF64A (5 nmole/2 microliters) produced a significant decrease in choline acetyltransferase (CAT) activity in the dorsal hippocampus (25%) and overlying frontoparietal cortex (30%) but no changes in the striatum. Rats lesioned with AF64A exhibited increased levels of open-field activity, which was most marked at 1 week after the lesion; however, the rates of intrasession habituation were similar in lesioned and control rats. Lesioned rats also displayed deficits in acquisition and retention of a passive avoidance task and less dramatic deficits in acquisition of two-way shuttle box avoidance. These findings indicate that lesioning of cholinergic terminals in the hippocampus and/or cerebral cortex with AF64A leads to long-term deficits in learning and memory as well as increases in open-field activity.

Animals↗

Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats.

Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

Amphetamine↗

Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice.

Neuromedin B (NMB) is a mammalian bombesin (BN)-like peptide that exerts its function via the neuromedin B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced by elevated blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhibited a marked reduction in memory performance. NMB-R-deficient mice exhibited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also observed between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced by electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.

Animals↗

Spatial discrimination, reversal and active or passive avoidance learning in rats with KA-induced neuronal depletions in dorsal hippocampus.

The neurotoxin kainic acid (KA) was iontophoretically administered to the dorsal hippocampus of female rats. Depending upon the diameter of the micropipette used to administered KA, this treatment completely depleted the dorsal hippocampus of nerve cell bodies (group LHC, N = 8) or selectively depleted CA4 (group SHC, N = 7) while sparing significant numbers of cells in CA1-CA3, and the fascia dentata. In both experimental groups, there was no apparent damage to the fimbria/fornix system, the ventral hippocampus and subiculum or neocortex adjacent to the injection site. The extensive neuron depletion (group LHC) sharply impaired the acquisition of a CAR in a shuttle box, produced a passive avoidance deficit in a step-through situation (but not in a punished-licking test), facilitated acquisition of a brightness discrimination in a T-maze, but had no significant effect on reversal learning in this situation. The more limited neuron depletions produced in group SHC produced no effect on CAR acquisition in the shuttle box but resulted in similar, though typically smaller effects in all other situations. The pronounced differences between this pattern of behavior change and that consistently reported after traditional lesions of the dorsal hippocampus indicate that damage to fibers of passage may contribute significantly to the classic hippocampal lesion syndrome.

Animals↗

Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats.

The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 micrograms/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 micrograms/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinch test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.

Animals↗

Effects of metrifonate on escape and avoidance learning in young and aged rats.

The present study assessed the effects of the indirect acetylcholinesterase inhibitor metrifonate on learning and memory functions in young (3-month-old) and aged (25-month-old) rats. In the shuttle box, metrifonate at a dose of 12.5mg/kg, p.o., 30min before each of the daily acquisition sessions, improved the acquisition of the active avoidance response, whereas a dose of 25mg/kg did not. Metrifonate, 12.5mg/kg, p.o., administered before each of the daily acquisition sessions, also facilitated the acquisition of the Morris water escape task in both young and aged rats: metrifonate-treated rats swam a shorter distance to reach the escape platform than did the vehicle-treated rats. The 3-month-old rats treated with metrifonate did not show the increase in swimming speed over training observed in vehicle-treated animals; no effects of metrifonate were found on the swimming speed of aged rats. In a probe trial carried out immediately after the fifth daily acquisition session, metrifonate treatment did not affect the bias of the aged rats for the quadrant in which the platform had been positioned during acquisition. It is concluded that metrifonate improves performance during the acquisition phase of two aversively motivated learning and memory tasks at the dose of 12.5mg/kg, p.o.

Journal Article↗

The role of differential reinforcement in predator avoidance learning.

Little is known about how predator recognition develops under natural conditions. Predispositions to respond to some stimuli preferentially are likely to interact with the effects of experience. Convergent evidence from several studies suggests that predator-nai;ve tammar wallabies (Macropus eugenii) have some ability to respond to vertebrate predators differently from non-predators and that antipredator responses can be selectively enhanced by experience. Here, we examined the effects of differential reinforcement on responses to a model fox (Vulpes vulpes), cat (Felis catus) and conspecific wallaby. During training, tammars experienced paired presentations of a model fox and a simulated capture, as well as presentations of a wallaby and a cat alone. Training enhanced responses to the fox, relative to the conspecific wallaby, but acquired responses to the two predators did not differ, despite repeated, non-reinforced presentations of the cat. Results suggest that experience interacts with the wallabies' ability to perceive predators as a natural category.

Journal Article↗

Impaired learning of active avoidance in water-intoxicated rats.

Brain edema is an important clinical condition. Pathophysiological findings on behavioral changes may be helpful for a comprehensive understanding of brain edema. However, only few reports on behavioral studies of brain edema have so far appeared. Experiments using psychological techniques on animals are rather time-consuming and may not be suitable for the study of transient conditions, as brain edema caused by trauma, vascular accidents, or others. We have developed a method for avoidance learning of rats using a running wheel apparatus with computer assistance. This model was employed in studies on brain edema from water introxication in rats. As a result, avoidance learning was significantly impaired by water intoxication. Either direct overhydration of the brain or indirect effects, as a decrease in cerebral blood flow, or both, are suggested as mechanisms underlying the impairment of behavior.

Animals↗

[Effects of low level toluene exposure during the developing stage of the brain on learning in high avoider rats].

THA (Tokai High Avoiders) rats were exposed in the exposure chambers to 100 and 500 ppm of toluene and air for 7 h every day from 13th day of gestation to 48 d of age. After the termination of toluene exposure, Sidman avoidance test was conducted on the rats for 10 d from 49 d of age (first test series), 100 d of age (second test series) and 150 d of age (third test series). The results obtained are as follows. No difference could be observed between the toluene exposed groups and controls in the initiation of pinna detachment, primary coat of downy hair, incisor eruption and eye opening. The body weight of the 100 ppm exposed group was slightly greater than that of the control and the 500 ppm exposed group. No difference was indicated between these three groups in reflex and locomotor activity. Avoidance learning: Avoidance rate in the two exposed groups of male rats was significantly lower than those in the control during the 60 min of the test in the first test series. The magnitude of individual variations of avoidance rate in the two exposed groups of male rats was also remarkably greater than that of the control. No difference was seen between the two exposed groups in both avoidance rate and magnitude of avoidance variation. In the second and third test series, the avoidance rate of the two exposed groups still did not attain the control levels during the period of the test series. In female rats, the avoidance rate of the two exposed groups during the first 30 min of the test in the first test series was slightly lower than the control. This difference in avoidance rate observed between the exposed groups and the control disappeared during the latter 30 min of the test. In the second and third test series, the avoidance rate of both exposed groups reached the control level during the test period. It may be concluded from the foregoing findings that 100 ppm and 500 ppm toluene exposure during the fetal and suckling periods affects learning in the rats after termination of the growth period, and that the learning disorder still remained as long as 100 days after the end of toluene exposure, although the effect decreased gradually. It was also observed that this learning disorder appeared more distinctly in male rats than in female rats.

Animals↗

Behavioral teratology of methylmercury.

Behavioral effects of experimental perinatal methylmercury exposure are reviewed. Studies were summarized by classification based on examined behaviors and functions as follows; Development of reflexive behaviors, Swimming ability, Spontaneous activity, Open-field behavior, Maze learning, Avoidance learning, Operant learning, Susceptibility to induced convulsion and seizure, Ultrasonic vocalization, Visual function. Findings suggest that perinatal methylmercury exposure caused changes in a wide spectrum of behaviors in offspring. It is suggested that further researches on neuro-behavioral teratogenicity of methylmercury will be awaited, especially in the area investigating interaction of the other environmental factors.

Animals↗