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PubMed1975

The effects of chloridazepoxide on avoidance performance of mice subjected to undernutrition or handling stress in early life.

This experiment compared the effects of (u) "early undernutrition" by rearing in large litters and (ii) an early handlin g stress, on avoidance learning in Swiss white mice. The two treatments, the first leading to permanent physical stunting and the second not, had similar and additive detrimental effects on avoidance performance. Treatment with the minor tranquillizer Chlordiazepoxide improved performance in all groups but had a proportionately greater effect on previously undernourished, handled mice. Thus the poor avoidance performace of mice reared in large litters appears to be largely independent of the growth stunting effect and more closely related to an elevated stress response produced by stress in early life.

Animals↗
PubMed1995

Learning-specific, time-dependent increase in [3H]phorbol dibutyrate binding to protein kinase C in selected regions of the rat brain.

Several lines of evidence indicate that protein kinase C (PKC) participates in long-term potentiation (LTP) and in certain forms of learning. Here we describe a rapid, specific and time-dependent increase in [3H]phorbol-12,13-dibutyrate ([3H]PDBu) binding to membrane-associated PKC in selected brain regions of rats submitted to an inhibitory avoidance task. A quantitative film autoradiographic method was used to determine the amount and distribution of membrane-bound PKC in rats sacrificed at various time intervals after training. At 0, 30 and 120 min following training there was a prominent increase (up to 200%) in the binding of [3H]PDBu throughout the hippocampus relative to naive, shocked or habituated control groups. No significant changes in [3H]PDBu binding in any brain region were found at 180 min after training. Similar training-specific increments in the binding of [3H]PDBu were observed in the frontal, parietal and entorhinal cerebral cortices, amygdala and cerebellum. The maximal effect was seen at 30 min in the CA2 region of the hippocampus (+200%) and at 30 and 120 min after training in the amygdala (+170%) in comparison to naive control values. No alterations in [3H]PDBu binding were found in the other brain regions studied. The present findings, together with previous data reporting a similar temporal course in the effects of intrahippocampal or intraamygdala infusion of specific PKC inhibitors on memory, suggest that PKC activation plays a role in the acquisition and consolidation of an inhibitory avoidance learning.

Analysis of Variance↗
PubMed1980

Differential effects of cholinergic blockade of anterior and posterior caudate nucleus on avoidance behaviors.

Groups of rats were trained in a one-trial passive avoidance task and then tested for retention 24 and 48 h later. They were also trained, in a single session, according to a one-way active avoidance paradigm. The effects of microinjections of atropine or of saline into the anterior caudate nucleus (CN) and of atropine into the posterior CN were assessed on these conditioned responses. Only those rats injected with atropine in the anterior CN showed a retention deficit in passive avoidance, while no effects on active avoidance became evident in any of the groups. These results suggest that cholinergic activity of the anterior CN is critically involved in memory consolidation of passive avoidance, but not in the processes mediating the acquisition of relatively simple active avoidance learning.

Animals↗
PubMed1993

Impairment of long-term potentiation and learning following chronic lead exposure.

Chronic lead exposure during brain development is known to affect functions of the central nervous system. We exposed rats chronically to low levels of lead at different developmental stages in order to determine the most sensitive periods of exposure. Active avoidance learning and hippocampal long-term potentiation were tested in the same animals. If the exposure period comprised the prenatal and the early postnatal phase and was continued into adulthood, learning as well as long-term potentiation were impaired. Starting the exposure not before 16 days postnatally, however, neither affected learning nor hippocampal potentiation. These results reflect the higher vulnerability of the immature as compared to the mature hippocampus to lead-induced functional deficits.

Animals↗
PubMed1996

Micro- and macrostructure of learning in active avoidance: a quantitative approach.

The dynamics of learning in the Active Avoidance test was analyzed at the trials level as well as at the level of daily sessions, each comprising numerous trials. The two scales (large scale for the sessions and small scale for the trials) were demonstrated to be mutually independent. The intermediate derived scales (blocks of trials) were found consistent among themselves and with small scale but independent of the large one. Moreover, the two extreme scales were kinetically discriminable. These results point to the existence of two independent mechanisms for large and small scale learning together with the need to postulate a consolidation process during the rest period.

Animals↗
PubMed2005

Noradrenaline involvement in the memory-enhancing effects of exposure to a complex rhythm stimulus following discriminated passive avoidance training in the young chick.

Previous research in our laboratory has demonstrated a significant memory-enhancing effect of exposure to a complex rhythm stimulus following weakly-reinforced passive avoidance learning in chicks. The aim of this study was to explore whether noradrenaline mediates this process. Chicks were trained on a strongly-reinforced single-trial passive avoidance task involving discrimination between two coloured beads. Intracerebral administration of the protein synthesis blocker, anisomycin, revealed that a phase of memory formation sensitive to arousal levels was extended by approximately 35 min following exposure to the complex rhythm stimulus. Administration of 2,4-dinitrophenol showed that this extension occurred during phase B of intermediate-term memory. Finally, a higher dose of the beta-adrenergic receptor antagonist, propranolol, was required to inhibit long-term memory in the presence of the auditory stimulus than in its absence. These findings suggest that the memory-enhancing effects of the complex rhythm stimulus may be mediated by noradrenaline, possibly via an increase in physiological arousal.

2,4-Dinitrophenol↗
PubMed1991

Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin.

In rats, pre- but not post-training ip administration of either flumazenil, a central benzodiazepine (BZD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil blocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effect. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, but it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that there is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory avoidance training or mere exposure to the training apparatus.

Animals↗
PubMed1969

Autoradiographic demonstration of biochemical changes in the limbic system during avoidance training.

After injection of leucine-H(3), members from eight triplets of rats were assigned to one of three treatment groups: avoidance learning, the same handling and shocks without opportunity to learn, or passive control. Autoradiographic grains over all nuclei were counted "blind." In the hippocampus, the number of grains for the learning rats was reliably greater than that for either control. The differences approached statistical significance in the entorhinal cortex and the septal area but not in other brain areas or in the liver. Although the processes responsible for the increased incorporation are not yet defined, these changes probably are the result of learning rather than of stress.

Analysis of Variance↗
PubMed1997

Transient, learning-induced ultrastructural change in spatially-clustered dentate granule cells of the adult rat hippocampus.

In semithin, Toluidine Blue-stained plastic coronal sections, we have observed hyperchromatic granule cells in the dorsal crest of the adult rat dentate gyrus following passive avoidance learning. These exhibited a time-dependent, twenty- to thirty-fold increase in their frequency at the 5-7 h post-training time. The hyperchromatic cells formed a rostral-caudal ribbon, 250 microns in diameter and 60 microns in depth, in sections obtained from -2.6 to -4.5 mm with respect to bregma. This was not observed in passive animals or yoked controls. Ultrastructural analysis revealed their cytoplasm and dendrites to be enriched in ribosomes and microtubules, respectively. Dendrites associated with the hyperchromatic cells exhibited a two-fold increase in spine number as compared to those of normochromatic cells in the same region of the dorsal mid-molecular layer. These changes are suggested to be associated with modulation of L1 and neural cell adhesion molecule-mediated neuroplastic change within this discrete post-training period of memory consolidation.

Animals↗
PubMed1991

Reversal of learning impairment in ventral globus pallidus-lesioned rats by combination of continuous intracerebroventricular choline infusion and oral cholinergic drug administration.

The effects of separate or combined oral administration of THA (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b] quinoline monohydrate hydrochloride) and intracerebroventricular choline infusion using an osmotic minipump were investigated by observing locomotor activity, shock sensitivity, passive avoidance response and cerebral choline and acetylcholine contents in the bilateral ventral globus pallidus-lesioned rat. Evaluation of locomotor activity and shock sensitivity revealed no sensorimotor disturbances caused by combined administration. Intracerebroventricular choline infusion (100 mumol/day) and oral THA or NIK-247 administration (0.5 mg/kg) had no effect on the acquisition of the passive avoidance response, while the combination of oral THA or NIK-247 administration (0.5 mg/kg) and intracerebroventricular choline infusion (100 mumol/day) elicited good acquisition of passive avoidance learning and produced a significant increase of choline and acetylcholine in the cerebral cortex of the bilateral ventral globus pallidus-lesioned rat. These findings suggest that continuous intracerebroventricular choline infusion may intensify the ameliorating effect of THA or NIK-247 on learning disturbance.

Acetylcholine↗
PubMed1978

Effects of extended training on rats depleted of central and/or peripheral catecholamines.

Thirty-two Wistar rats were used to investigate the effects of extended training on avoidance performance of rats depleted of Catecholamines. They were injected with 6-hydroxydopamine either (i) intracisternally, (ii) intraperitoneally, or (iii) both IP and IC, and trained on the two-way shuttlebox avoidance task. The results on peripheral noradrenaline depletion led to the conclusion that extended training ameliorates the observed behavioural deficit significantly back to the level of controls. The conclusion that is indicated by the present central catecholamine depletion are: (i) central catecholamine depletion has long term effect on behavioural deficit, (ii) central depletion is more detrimental to avoidance learning than peripheral depletion, and (iii) plasma corticosterone plays no significant mediating roles.

Animals↗
PubMed2001

[Effects of pre-exposure to an experimental chamber on memory trace retrieval in aggressive and submissive mice during extinction of conditioning].

Mice with a submissive stereotype of behaviour developed a fast habituation to novelty of environment. A subsequent training revealed a deficit of passive avoidance learning and prolongation of the memory trace extinction. Aggressive mice are characterised by a delay of the habituation and absence of any significant changes in the memory trace retrieval. The findings suggest that responses to environmental novelty and use of its estimation in learning and retention of memory traces are essentially predetermined by the basic strategy of behaviour.

Aggression↗
PubMed1998

Effects of vanadium on activity and learning in rats.

The effects of vanadate administration on activity and learning were assessed in rats. Four groups of adult male rats were given by gavage 0, 4.1, 8.2, and 16.4 mg/kg/day of sodium metavanadate for eight consecutive weeks. Three weeks after the cessation of the treatment, general motor activity of all animals was measured in an open-field. Rats were also tested for two-way shock avoidance learning in an automatic reflex conditioner. At the end of the testing period, rats were killed and vanadium concentration was determined in a number of tissues. Vanadium exposure caused an observable but not significant effect on body weight gain, while a persistent presence of vanadium was observed in all tissues measured. The results of the behavioral testing show that oral vanadate administration resulted in significant reductions in both general activity and learning.

Animals↗
PubMedDate not supplied

[Modulation of behavior of mice of different genotypes by serotonin antibodies].

The effect of active immunization with conjugated serotonin-protein on the "open-field" behaviour and passive avoidance conditioning was studied in genetically different mice strains (C57BL/6 and BALB/c). The obtained immunophysiological effects of serotonin antibodies depended on genetically determined characteristics of animal behaviour. Serotonin antibodies altered rearing and crossings of the "open-field" center and retention of passive avoidance learning in C57BL/6 mice. The active immunization with conjugated serotonin-protein of BALB/c mice resulted in modulation of the "open-field" latency and both training and testing of passive avoidance behaviour.

Animals↗
PubMed1977

Effects of pimozide on the acquisition, maintenance, and extinction of an amphetamine-induced taste aversion.

Different groups of rats were pretreated with the dopamine receptor blocker, pimozide (0.25, 0.5, or 1.0 mg/kg), in an attempt to investigate the role of dopaminergic transmission in the acquisition, maintenance, and extinction of a taste aversion produced by d-amphetamine dulphate (1.0 or 2.0 mg/kg). In the first phase of the experiment, all doses of pimozide attenuated but did not block the acquisition of the aversion produced by 1.0 mg/kg but not by 2.0 mg/kg amphetamine. In Phase II, pimozide pretreatment was suspended to allow the attenuated groups to acquire the aversion and then reintroduced in Phase III. In this phase all groups continued to avoid the taste, indicating a failure of pimozide to affect the maintenance of the avoidance response. When amphetamine treatment was suspended in Phase IV, pimozide accelerated the extinction, especially in those groups that had previously received the 1.0 mg/kg dose of amphetamine. These results are discussed with reference to dopaminergic mechanisms in avoidance learning and a pimozide-mediated reduction in the functional strength of amphetamine as an unconditioned stimulus.

Animals↗
PubMedDate not supplied

Prenatal alcohol exposure alters hippocampal slice electrophysiology.

Pregnant Sprague-Dawley rats consumed an ethanol-containing liquid diet containing 0%, 17.5% or 35% ethanol-derived calories (EDC) from gestation day 8 until parturition. A fourth group was fed standard rat chow as an ad lib diet control. Animals prenatally exposed to ethanol had lower birth weights and impaired passive avoidance learning at 17 days of age. At 90 days of age synaptic potentials in area CA1 were characterized electrophysiologically in hippocampal slices. Slices from ethanol-exposed rats had significantly greater paired-pulse facilitation compared to 0% EDC and ad lib controls. Histological examination of brains from litter mates did not indicate altered number, density or nuclear volumes for neurons in area CA1. These data indicate that prenatal ethanol exposure can result in abnormal hippocampal synaptic physiology and suggest that these changes may contribute to the learning impairments observed in rats following such exposure.

Animals↗
PubMed2002

Passive avoidance training enhances cell proliferation in 1-day-old chicks.

One-day-old domestic chicks were injected i.p. with bromodeoxyuridine (BrdU) before training on a one-trial passive avoidance task where the aversive experience was a bead coated with a bitter tasting substance, methyl anthranilate (MeA). Animals were tested 24 h later; those avoiding (if MeA-trained) or pecking if water (W)-trained (which they peck appetitively), along with a group of untrained naïve chicks, were used to determine cell proliferation either 24 h or 9 days post BrdU injection. In all three groups, BrdU positive cells were identified sparsely throughout the forebrain but labelling was pronounced around ventricular zone (VZ) surfaces at both 24 h and 9 days post-BrdU-injection. Double immunolabelling with neuronal specific antibodies, to either NeuN, or beta-tubulin III, confirmed that most BrdU labelled cells appeared to be neurons. Unbiased stereological analysis of labelled cells in selected forebrain areas 24 h post BrdU injection showed a significant MeA-training induced increase in labelled cells in both the dorsal VZ surface bordering the intermediate and medial hyperstriatum ventrale (IMHV) and the tuberculum olfactorium (TO). By 9 days post-BrdU-injection, there was a significantly greater number of BrdU labelled cells in MeA-trained birds within the IMHV, lobus parolfactorius (LPO) and TO. These results demonstrate that avoidance training in 1-day-old chicks has a marked effect on cell proliferation, in the LPO and IMHV, regions of the chick previously identified as a key loci of memory formation, and in a second region (TO), which has olfactory functions, but has not been previously investigated in relation to avoidance learning.

Animals↗