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PubMedDate not supplied

[Changes in brain serotonin metabolism and [3H]-serotonin receptor binding during recall of conditioned passive avoidance in rats].

The content of serotonin and its metabolite 5-hydroxyindoleacetic acid, monoamine oxidase activity, and [3H]-serotonin radioligand receptor binding were examined in the prefrontal cortex, striatum, amygdala, hippocampus and periaqueductal gray matter at different time after one-trial passive avoidance training of rats. Changes in the serotonergic activity were observed only in rats, which showed retrieval of conditioned passive avoidance response. No serotonergic changes were found immediately and one day after training. Also, there were no changes in trained rats without retrieval of conditioned passive avoidance response or rats with experimental amnesia. The pattern of the involvement of brain structures in the retrieval process was also revealed. [3H]-serotonin binding was decreased in the amygdala, periaqueductal gray matter and striatum, whereas it did not change in the prefrontal cortex and hippocampus. At the same time, the serotonin content in these structures did not differ from that of intact rats. Deamination of serotonin by monoamine oxidase and active transport of 5-hydroxyindoleacetic acid from nerve terminals were increased in the amygdala and periaqueductal gray matter, whereas in the striatum serotonin catabolism was decreased. The obtained differences in serotonin catabo- lism suggest that the decrease in receptor binding of serotonin in these brain structures is provided by different synaptic processes: presynaptic changes in the striatum and postsynaptic receptor changes in the amygdala and periaqueductal gray matter. It is concluded that the decrease in the serotonergic activity in the amygdala and periaqueductal gray matter represents one of the mechanisms activating the emotiogenic system mediating the memory trace retrieval in inhibitory avoidance learning.

Amygdala↗
PubMed1988

Investigation into sex-related differences in locomotor activity, place learning and passive avoidance responding in NMRI mice.

Learning abilities of young adult (5-6 weeks) male and female NMRI mice were compared in two tasks involving cognitive functions, namely spatial learning in a water maze and passive avoidance responding. Locomotor activity was also monitored as a putative bias for the results obtained in these learning tests. No sex-related difference was observed either in avoidance responding or in spatial learning using a procedure with the same point of departure throughout testing in the water maze. However, in this test, using a procedure with 3 different points of departure in randomized order day after day, female mice performed better than male mice. The difference was statistically significant on the last acquisition day but was not sustained during a retention trial 72 hr later. Since no sex differences in locomotor activity were observed, the learning effects cannot be attributed to a difference in general activity level.

Animals↗
PubMed1977

Early environmental influences on conditioned and unconditioned ingestional and locomotor behaviors.

For 34-44 days after weaning one group of rats was raised in a socially enriched environment, whereas another group was raised in isolated individual cages without handling. Following this differential rearing subjects were tested for ingestional neophobia and its attenuation, enhancement of ingestional neophobia by aversive drug administration, taste-aversion learning and extinction, open-field activity, and passive shock-avoidance learning. Although the differential rearing influenced open-field activity and shock-avoidance this manipulation did not have a significant effect on the various measures of conditioned and unconditioned ingestional behaviors. The results provide further evidence for the distinctiveness of gustatory-visceral and telereceptor-cutaneous sensory systems.

Animals↗
PubMed1996

Successive negative contrast in one-way avoidance: effect of thiopental sodium and chlorpromazine.

The successive negative contrast effect on one-way avoidance was induced by shifting rats from a large reward (30 s spent in the safe compartment after completion of the avoidance response, pre-shift phase) to a small reward (1 s, post-shift phase). Under these conditions, the previously learned avoidance response deteriorated (negative contrast) when compared to a control group for which 'safe time' remained constant throughout the experimental situation (1 s). Thiopental sodium at a dose of 5 or 10 mg/kg, but not at 1, 2, 15 or 20 mg/kg i.p., abolished the negative contrast effect, and did not affect performance of the one-way avoidance task. Similar results were found when rats were treated with diazepam (1 mg/kg i.p.). Chlorpromazine at a dose of 0.5 or 1 mg/kg i.p. did not affect negative contrast, although at higher doses (2 or 3 mg/kg) there was an increase in the number of trials needed to reach the criterion for learning the avoidance response. This increase was evident in both pre-shift and post-shift phases, although only in the experimental situations involving a low level of reinforcement (1 s in the safe compartment). On the basis of these results, we tentatively suggest that the successive negative contrast effect in one-way avoidance in rats can be considered a useful pharmacological animal model for research into anxiety.

Animals↗
PubMed1998

Learning-specific, time-dependent increases in hippocampal Ca2+/calmodulin-dependent protein kinase II activity and AMPA GluR1 subunit immunoreactivity.

Ca2+/calmodulin-dependent protein kinase II (CAMK II) and one of its target, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), glutamate receptors have been shown to participate in both long-term potentiation (LTP) in the hippocampus, and in spatial, as well as in a variety, of learning paradigms. Recently, we were able to demonstrate that the intrahippocampal infusion of a specific inhibitor of CAMK II (KN62) provoked full retrograde amnesia of an inhibitory avoidance learning in rats when given immediately, but not 120 or 240 min, after training. Furthermore, this task is accompanied by a rapid, selective and reversible increase in hippocampal [3H] AMPA receptor binding. Here we report the effect of this aversively motivated learning task on CAMK II activity, and AMPA GluR1 subunit phosphorylation and immunoreactivity in the hippocampus. One trial inhibitory avoidance training is associated with a learning-specific, time-dependent increase (25-78%) in both total and Ca2+-independent activities of CAMK II in the hippocampus of rats killed immediately (0 min), but not 120 min, after training. In addition, immunoblotting experiments showed an increment in the amount of the alpha-subunit of CAMK II at 0, 30 and 120 min after training. An increase in the in vitro phosphorylation of alpha- and beta-subunits of CAMK II was also observed in hippocampal synaptosomal membranes (SPM) of trained rats killed immediately and 30 min post-training. In addition, inhibitory avoidance is accompanied by a 20% increase in GluR1 phosphorylation and a 33% increase in GluR1 immunoreactivity 120 min after training. No significant changes were observed in shocked animals. Phosphorylation of hippocampal SPM from naive control animals in conditions suitable for CAMK II activation resulted in a large increase in the density of [3H] AMPA binding (+ 100%). Taken together, these findings confirm and extend previous data suggesting that CAMK II and AMPA glutamate receptors in the hippocampus participate in the early phase of memory formation of an inhibitory avoidance learning.

Animals↗
PubMed1997

Prevention of amitriptyline-induced avoidance impairment by tacrine in mice.

The effects of two cognition enhancers on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box avoidance acquisition and in previously trained mice of the DBA/2 strain. The nootropic agent piracetam (50, 100 or 200 mg/kg, i.p.) had slight or no effect in mice receiving amitriptyline (5 or 10 mg/kg, i.p.). Conversely, the acetylcholinesterase inhibitor tacrine (0.5, 1, 2 or 3 mg/kg, i.p.) prevented the avoidance impairment induced by 5 mg/kg amitriptyline on shuttle-box avoidance acquisition as well as on a previously learned avoidance response. The avoidance disrupting action produced by 10 mg/kg of the antidepressant drug was not affected by the anticholinesterase drug. The preventing action of tacrine seems specifically related to the avoidance impairment induced by amitriptyline, since the acetylcholinesterase inhibitor did not reduce, but enhanced the avoidance impairing action of the neuroleptic chlorpromazine. Taken together, the results indicate that amitriptyline-induced avoidance impairment, and the related preventing action of tacrine, may be ascribed to drug effects on the performance of the avoidance response, rather than to interferences with learning processes.

Amitriptyline↗
PubMedDate not supplied

[The dependence of learning an active avoidance reaction on overcoming a problem-solving situation in a shuttle box].

The two-way avoidance procedure dramatically differs from the one-way procedure in rate of learning. The present study was conducted to prove that retardation of the two-way avoidance acquisition resulted from development of the behavioral conflict tendency not to reenter the previous shock compartment. Cluster analysis of avoidance response indices divided rats into three distinctive classes. The occurrence of avoidance, escape, and freezing responses in the first session was analyzed in these three groups. Freezing during the shock action reflected the conflict tendency and showed a negative correlation with avoidance response indices. Only the rats which overcame the conflict and performed at least one avoidance reaction toward the end of the first session significantly improved their avoidance score in the following session. Discriminant analysis of indices of the three reaction types in the first session revealed sufficiency of these indices for prediction of the success in avoidance learning in subsequent sessions. Our results proved the hypothesis formulated previously that the conflict situation inherent to the two-way shuttle box procedure retarded the active avoidance acquisition. A number of trials have to be reserved in the first session for solving the conflict situation (direct effect on the rate of learning). The conflict intensity which directly effects the avoidance performance in the first session, presumably, influences learning in subsequent sessions (secondary effect on learning).

Animals↗
PubMed1991

Disturbance of learning and memory by the alkylation of muscarinic acetylcholine receptors by propylbenzilylcholine mustard.

The effects of blockade of muscarinic acetylcholine receptors (mAChR) in rat cerebral cortex on learning and memory were studied by the use of passive and active avoidance tests. Injection of propylbenzilylcholine mustard (PrBCM) into frontal, parietal and occipital cortex decreased mAChR dose dependently, as assessed by 3H-quinuclidinylbenzilate binding studies. Bilateral injection of PrBCM into frontal and/or parietal but not occipital cortex impaired passive avoidance learning. The results suggest that intact muscarinic neurotransmission is important for registration and recall, but not retention phases of the learning and memory process. Alkylation of mAChR by PrBCM also caused impairment in the performance of active avoidance task.

Alkylation↗
PubMed1985

Nicotine-produced relearning deficit in C57BL/6J and DBA/2J mice.

Acute nicotine administration has been shown to influence the acquisition and retention of learning tasks. In order to investigate the many possible behavioral and pharmacological effects of nicotine, a modified 2 X 2 state-dependent learning design was used to assess nicotine's effects on active avoidance learning. Male and female mice of the C57BL/6J (C57) and DBA/2J (DBA) inbred strains were injected with a control solution or with 0.5, 1.0, or 2.0 mg/kg nicotine 5 min before the start of training and, following a 24-h period, 5 min before retraining. Nicotine had no effect on the acquisition of the learning task but, depending on strain and sex, did have an effect on relearning. Relearning in the C57 males was unaffected by nicotine injection, whereas the most prominent effect of nicotine in the C57 females and the DBA males and females was a retrieval deficit. The prevalence of a nicotine-induced retrieval deficit in the present experiment suggests that those mechanisms underlying the retrieval of previously learned information are, in part, mediated or modulated by perturbations within nicotine-sensitive areas of the central nervous system.

Animals↗
PubMed2006

Learning induces long-term potentiation in the hippocampus.

Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown that learning actually induces LTP in CA1. We found that one-trial inhibitory avoidance learning in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS and caused a spatially restricted increase in the amplitude of evoked synaptic transmission in CA1 in vivo. Because the learning-induced synaptic potentiation occluded HFS-induced LTP, we conclude that inhibitory avoidance training induces LTP in CA1.

Animals↗
PubMed1999

Attenuation by nimodipine of amitriptyline-induced avoidance impairment in mice.

The effects of the dihydropyridine calcium channel blocker nimodipine on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box training and in previously trained mice of the DBA/2 strain. Nimodipine (0, 0.5, 1, 2.5, or 5 mg/kg) had no effect alone, but attenuated the avoidance impairment induced by 5 mg/kg amitriptyline on avoidance acquisition, as well as on a previously learned avoidance response. The avoidance improving action of the calcium channel blocker was less evident in mice receiving a larger dose (7.5 mg/kg) of the antidepressant drug. The effect of nimodipine did not appear to be specifically related to the avoidance impairment induced by amitriptyline, because the calcium antagonist also attenuated the avoidance impairing action of the neuroleptic chlorpromazine. The avoidance impairment induced by amitriptyline and chlorpromazine, and the related ameliorating action of nimodipine, seem imputable to drug effects on the performance of the avoidance response, rather than to interferences with learning processes. The results suggest that, in the case of concomitant administration, nimodipine could alleviate adverse side effects of tricyclic antidepressant, i.e., psychomotor disturbances.

Amitriptyline↗
PubMedDate not supplied

[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.

Animals↗
PubMed2002

[The dynamics of neuronal, autonomic and movement parameters in animals during the reproduction of a learned habit].

Data by the authors, as well as from other laboratories, show that the intertrial responses correlated with accuracy of avoidance or feeding behaviour. Moreover our previously data demonstrated the definite changes of neuronal activity, heart rate and respiration during intertrial responses. In this study we investigated the time-course of intertrial response appearance, the pattern of neurophysiological parameters during intertrial periods, and the types of intertrial responses. Experiment 1 showed that different environmental stimuli influenced the level of intertrial responses and successfulness of the avoidance learning. In experiment 2, in which learning and extinction procedures were presented in rabbit passive-avoidance conditioning, two types of intertrial responses were observed; the first type repeated the pain reinforcement, the second one imitated the conditioned reaction of neuronal activity, heart rate, respiration, and moving. These investigations suggest that the processes of intertrial eliciting of avoidance effector programs may be one of the mechanisms of fixation in memory and play an important role in acquisition of more effective results.

Acoustic Stimulation↗
PubMed1998

Prenatal exposure to cocaine impairs neuronal coding of attention and discriminative learning.

Cingulate cortex and related areas of the thalamus are critically involved in the mediation of discriminative avoidance learning, wherein rabbits step in response to an acoustic conditional stimulus (CS+) to avoid foot shock and they learn to ignore a different acoustic stimulus (CS-) not followed by shock. Studies of multi-unit neuronal activity recorded simultaneously in many cingulothalamic areas have documented massive learning-related neuronal firing changes during the course of behavioral acquisition. Stimulated by findings (this volume) of neurobiological changes in anterior cingulate cortex in rabbits exposed in utero to cocaine, we investigated behavioral learning and correlated neuronal activity in several cingulothalamic areas in cocaine-exposed rabbits. In an initial study, training-induced enhancement of cingulate cortical neuronal firing in response to the CS+ and CS- was abolished in rabbits exposed to cocaine in utero. Yet discriminative neuronal activity (greater firing in response to the CS+ than to the CS-) did develop during training, and behavioral learning was normal in the cocaine-exposed rabbits. In a second study, we reduced the salience of the CS+ and CS- by employing 200 msec CSs rather than standard 500 msec CSs. Early training-stage development of anterior cingulate cortical discriminative neuronal activity was abolished, the elicited neuronal discharge profiles were altered, and behavioral learning was impaired in rabbits exposed to cocaine, relative to saline-exposed controls. The specificity of these changes to low-salience CSs suggested that prenatal cocaine results in disturbed associative attentional processes of anterior cingulate cortex in adult rabbits. Consideration of the neuronal response profile alterations together with other reported neurobiological changes suggested that the cocaine-related attentional deficit is due to impaired dopaminergic afferent activation of GABA neurons in anterior cingulate cortex.

Acoustic Stimulation↗
PubMed1995

Effects of footshock-, psychological- and forced swimming-stress on the learning and memory processes: involvement of opioidergic pathways.

Modulation of learning and memory acquisition, retention and retrieval in the one trial passive avoidance learning task in mice by three inescapable stresses, i.e., footshock (FS), psychological (PSY) and forced swimming (SW) were investigated. Pre-, post-training and pre-test FS-stress (2 mA, 0.2 Hz, 1 sec for 30 min) and pre-training PSY-stress (communication box, 5 min) resulted in enhanced test latencies. On the contrary, SW-stress (20 degrees C, 5 min) immediately or 1 hr after training impaired retention latencies that tended to recover after 2 hr post-training SW-stress, suggesting that at least 2 hr are required to consolidate newly acquired information. In contrast, pre-stress naloxone (Nx), which did not affect FS- and PSY-stress induced facilitatory effects, returned to control levels the impaired retention latencies induced by SW-stress. Taken collectively, these results imply the involvement of an opioid-dependent mechanism in the modulation of memory by SW-stress and non-opioid in the case of FS- and PSY-stress. Furthermore, they suggest that different mechanisms are involved in stress-induced memory modifications and the production of stress-induced analgesia (SIA) since in the latter, FS and PSY but not SW stress produce Nx-sensitive antinociception.

Animals↗
PubMed1980

Pavlovian excitation, internal inhibition, and their interaction with free operant avoidance as a function of age in rats.

The central hypothesis was that, in young as compared with adult rats. Pavlovian excitation is weaker and extinguishes more slowly, whereas internal inhibition is weaker but extinguishes more rapidly. In Experiment I, the suitability of free operant (Sidman) avoidance as a baseline for measuring Pavlovian effects was assessed in 5 age groups between 19 and 98 days of age trained in a shuttle box. Although clear age-related increases were evident in avoidance capacity, efficient "high criterion" avoiders were found in all age groups, indicating that the response was suitable. In Experiment II, groups of 26-, 38-, and 95-day-old rats first received Pavlovian aversive excitatory and differential inhibitory conditioning, or the conditional stimuli and shock randomly, or no treatment. Three days later they received free avoidance training. Prior Pavlovian conditioning facilitated subsequent avoidance learning in young subjects, but depressed it in adults. Among "high criterion" avoiders, such effects were absent. Following the avoidance training phase, 3 age groups of matched "high criterion" avoiders received conditioned stimuli superimposed on the baseline (a conditioning test). These results confirmed the central hypothesis.

Age Factors↗
PubMed1978

Avoidance behavior in folate--deficient rats.

The effects of folate deficiency in post-weanling male rats in an active avoidance learning test were studied. Ingestion of a folate-free diet for 3 weeks markedly decreased serum and erythrocyte folate concentrations but had only a slight effect on growth rate. The decrease in blood folates was correlated with an increase in the number of trials necessary to reach criterion in the learning test. There was no motor impairment since the mean escape latency was the same in control and folate-deficient animals. These results suggest that folic acid deficiency started at weaning could be responsible for learning impairment.

Animals↗