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PubMed2006

Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm.

Colostrinin (CLN) is a biologically active proline-rich polypeptide which has therapeutic potential for the alleviation of memory deficits in age-related dementias in a number of human conditions, particularly Alzheimer's disease. To examine the efficacy of CLN in other species, day-old domestic chicks were used as a model system to study its effects on retention of memory for a single one-trial learning paradigm--avoidance of a bitter-tasting substance (methylanthranilate, MeA). Birds were presented with a bead coated with either a dilute (10%) solution of MeA or a bead coated with 100% MeA. Those trained on 100% MeA avoided pecking at a similar but dry bead 24 h later, thereby demonstrating long-term memory whereas chicks trained on the 10% solution pecked the bead at 24 h, indicating lack of long term memory for the task. However, when CLN was injected (i.c.) into a region known to be important in memory formation, the mesopallium intermediomediale (IMM), prior to training with 10% MeA, chicks exhibited strong memory retention at 24 h, similar to those trained on 100% MeA. Control chicks trained on 10% MeA but injected i.c. with a 10% saline solution did not show improvement in memory retention. Intraperitoneal (i.p.) injections of CLN were as effective as the i.c. route. These data extend the known efficacy of CLN from mammals demonstrating its widespread efficacy as a cognitive enhancer.

Animals↗
PubMedDate not supplied

Food avoidance learning in squirrel monkeys and common marmosets.

Using a conditioned food avoidance learning paradigm, six squirrel monkeys (Saimiri sciureus) and six common marmosets (Callithrix jacchus) were tested for their ability to (1) reliably form associations between visual or olfactory cues of a potential food and its palatability and (2) remember such associations over prolonged periods of time. We found (1) that at the group level both species showed one-trial learning with the visual cues color and shape, whereas only the marmosets were able to do so with the olfactory cue, (2) that all individuals from both species learned to reliably avoid the unpalatable food items within 10 trials, (3) a tendency in both species for quicker acquisition of the association with the visual cues compared with the olfactory cue, (4) a tendency for quicker acquisition and higher reliability of the aversion by the marmosets compared with the squirrel monkeys, and (5) that all individuals from both species were able to reliably remember the significance of the visual cues, color and shape, even after 4 months, whereas only the marmosets showed retention of the significance of the olfactory cues for up to 4 weeks. Furthermore, the results suggest that in both species tested, illness is not a necessary prerequisite for food avoidance learning but that the presumably innate rejection responses toward highly concentrated but nontoxic bitter and sour tastants are sufficient to induce robust learning and retention.

Animals↗
PubMed2006

Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain.

Avoidance learning poses a challenge for reinforcement-based theories of instrumental conditioning, because once an aversive outcome is successfully avoided an individual may no longer experience extrinsic reinforcement for their behavior. One possible account for this is to propose that avoiding an aversive outcome is in itself a reward, and thus avoidance behavior is positively reinforced on each trial when the aversive outcome is successfully avoided. In the present study we aimed to test this possibility by determining whether avoidance of an aversive outcome recruits the same neural circuitry as that elicited by a reward itself. We scanned 16 human participants with functional MRI while they performed an instrumental choice task, in which on each trial they chose from one of two actions in order to either win money or else avoid losing money. Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance.

Adult↗
PubMedDate not supplied

The role of nitric oxide in passive avoidance learning.

The role of nitric oxide on passive avoidance learning was studied by administering L-arginine or D-arginine to male rats in a passive avoidance paradigm. L-Arginine administered into the lateral brain ventricle at a dose of 1.25 microg showed a tendency to increase the passive avoidance latency, and 2.5 microg exerted almost maximal action, but the action gradually increased still further up to 20 microg tested. D-Arginine had no action. Peripheral administration (intraperitoneal) of L-arginine facilitated the consolidation of passive avoidance learning in a dose-dependent manner. A significant increase in passive avoidance response was obtained following an injection of 100 mg/kg L-arginine. When L-arginine was given i.c.v. with a selected dose of 5 microg, 30 min prior to a learning trial, the latency of the passive avoidance response was likewise lengthened. However, when L-arginine was given 30 min before the 24-hr testing (retrieval), it was ineffective. It was also ineffective when given 6 hr after the training trial. However, when L-arginine was administered immediately following the training trial, the action in improving the consolidation could be detected 6 hr after the training trial. Nitro-L-arginine, which blocks nitric oxide synthase, can also block the facilitation of consolidation caused by the nitric oxide donor L-arginine. The nitric oxide synthase inhibitor per se in different doses had no action on the learning of a passive avoidance task. The results indicate that nitric oxide is able to facilitate the learning and consolidation of memory in a passive avoidance paradigm, but it is ineffective in retrieval processes. The results also suggest that, under the experimental circumstances used, nitric oxide is involved only in the facilitated learning and memory processes caused by pharmacological effect of L-arginine, and not involved in normal learning processes.

Animals↗
PubMed1988

Opposite effects induced by low and high doses of apomorphine on single-trial passive avoidance learning in mice.

The effects of apomorphine (0.0125-1 mg/kg, SC), a dopamine (DA) agonist, on passive avoidance learning were assessed in mice which received brief and long foot-shocks in a training test. At low doses, apomorphine stimulates DA autoreceptors. With a shock of brief duration, apomorphine at a low dose (0.05 mg/kg), enhanced the avoidance learning when it was administered 20 min before the training test or the retention test. At high doses, apomorphine stimulates postsynaptic DA receptors. With a shock of long duration, apomorphine at a high dose (1 mg/kg), impaired the avoidance learning when it was administered 20 min before the training test or the retention test. However, apomorphine (0.05 and 1 mg/kg) given immediately after the training test did not have any effect on the avoidance behavior with shocks of either brief or long durations. Apomorphine-induced enhancement of passive avoidance learning was antagonized by sulpiride, but not by haloperidol. These results show that apomorphine induced the opposite effects on the passive avoidance learning depending on the dose or on the reinforcement intensity and suggest that the central DA system may play an important role in modulating memory processes.

Animals↗
PubMed2004

Lesions of the medial pallium, but not of the lateral pallium, disrupt spaced-trial avoidance learning in goldfish (Carassius auratus).

The effects of telencephalic lesions of the medial pallium (MP) and lateral pallium (LP) of goldfish on avoidance learning were studied in a two-way, shuttle response, spaced-trial avoidance conditioning situation. Animals received one trial per day, a training regime that permits the assessment of avoidance learning in the absence of stimulus carry-over effects from prior trials. Control and LP-lesioned goldfish exhibited significantly faster avoidance learning than MP-lesioned animals. These results suggest that the MP, but not the LP, is responsible for the widely described deficits in avoidance learning after lesions of the entire telencephalon. The proposal of a functional similarity between the fish MP and the mammalian amygdala, known to be involved in fear conditioning, suggests a conservative phylogenetic role of this area in avoidance learning.

Animals↗
PubMed1979

Postnatal alpha-methylphenylalanine treatment effects on adult mouse locomotor activity and avoidance learning.

Neonatal mice were injected for five days with a combination of alpha-methylphenylalanine and phenylalanine to determine the influences of excess phenylalanine during development upon the behavior of these mice as adults. Spontaneous activity, bolus production, passive avoidance learning, simple active avoidance learning and complex active avoidance learning were tested in mice treated at two different postnatal periods. The results show that the treatments during development produced adult behavioral alterations compared to controls. The effects were most pronounced in mice treated in the postnatal period immediately after birth. The behavioral effects can be summarized as increased emotionality and generalized, stimulus-induced activity as well as decreased passive avoidance performance and complex active avoidance performance. These behavioral deficits are consistent with those usually reported in various models of human phenylketonuria.

Animals↗
PubMed2004

Context preexposure influences the effectiveness of feedback stimuli in avoidance learning.

According to the effective reinforcement theory of avoidance learning, there is a positive relationship between the level of context fear and the effectiveness of feedback stimuli. The present research used different preexposure treatments to manipulate context fear and to evaluate the effects of feedback stimuli in two-way avoidance learning. Rat subjects received nonreinforced preexposure either to the nonvisual context cues (avoidance apparatus with the houselights extinguished), to the visual context cues (avoidance apparatus with the houselights on but with a Plexiglas floor covering the grids), or to a neutral box. During subsequent avoidance training conditioned stimulus termination was delayed for 5s after an instrumental response and either a flashing light or darkness was presented as a feedback stimulus. Without preexposure, darkness produced better avoidance performance than did the flashing light. Preexposure to the visual context cues decreased the effectiveness of darkness as a feedback stimulus. However, preexposure to either the visual or to the nonvisual context cues facilitated avoidance performance when a flashing light was used as a feedback stimulus. The results suggest that the effects of a feedback stimulus may be dependent upon the amount and source of context fear.

Animals↗
PubMed2002

Involvement of mu(1)-opioid receptors and cholinergic neurotransmission in the endomorphins-induced impairment of passive avoidance learning in mice.

The effects of naloxonazine, a mu(1)-opioid receptor antagonist, and physostigmine, a cholinesterase inhibitor, on the endomorphins-induced impairment of passive avoidance learning were investigated in mice. Endomorphin-1 (10 microg) and endomorphin-2 (10 microg) significantly impaired passive avoidance learning, while naloxonazine (35 mg/kg, s.c.), a mu(1)-opioid receptor antagonist, which alone failed to influence passive avoidance learning significantly inhibited the endomorphin-1 (10 microg)- but not endomorphin-2 (10 microg)-induced disturbance of such learning. A rather nonselective higher dose (50 mg/kg, s.c.) of naloxonazine almost completely antagonized the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced impairment of passive avoidance learning. In contrast, physostigmine (0.025 and 0.05 mg/kg, i.p.) significantly reversed the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced disturbance of passive avoidance learning, whereas physostigmine (0.025 and 0.05 mg/kg, i.p.) alone did not influence such learning. These results suggest that endomorphin-1 but not endomorphin-2 impairs learning and memory resulting from cholinergic dysfunction, and from activation of mu(1)-opioid receptors.

Animals↗
PubMed2000

Immunohistochemical estimation of brain choline acetyltransferase and somatostatin related to the impairment of avoidance learning induced by thiamine deficiency.

We have found that thiamine-deficient (TD) rats show significant impairment of avoidance learning on the 25th day after the start of TD diet, as measured by passive-avoidance task. Administration of physostigmine (0.1 mg/kg, i.p.) from the 14th day after the start of TD diet improved the impairment of avoidance learning to the pair-fed (PF) control level by the 25th day. However, the recovery effect of physostigmine did not occur on the 25th day when the treatment was begun on the 21st day. To ascertain the correlation between the cholinergic neuronal function in rat brain and the avoidance learning impairment induced by TD, the immunohistochemical distribution of brain choline acetyltransferase (ChAT) was determined by fluorescence intensity using two-dimensional microphotometry. The intensity of the ChAT fluorescence started to decrease in the cortex and hippocampus on the 14th day and showed a marked decrease in the cortex, hippocampus and thalamus on the 25th day of TD feeding in comparison with PF controls. The intensity of the somatostatin (SST) fluorescence was unchanged on the 14th day of TD feeding, but on the 25th day, SST was significantly decreased in comparison with PF controls. Furthermore, physostigmine treatment from 14th day after the start of TD diet reversed SST fluorescence intensity to the control level by the 25th day. These results suggest that the impairment of avoidance learning induced by TD may involve not only cholinergic but also somatostatinergic systems.

Amygdala↗
PubMed2007

Roles of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II in inhibitory avoidance learning in rats.

This study investigated the interactive roles of nitric oxide and calcium/calmodulin-dependent protein kinase II in inhibitory avoidance learning. In Experiment I, rats were trained on a one-trial step-through inhibitory avoidance learning task, whereas the controls were trained in a noncontingent stimulus-pairing condition. The experimental rats showed significantly higher retention scores than the control rats. Correspondingly, the rats in the experimental group showed significantly higher Ca2+-independent activity of the hippocampal calcium/calmodulin-dependent protein kinase II and a significant increase in the endogenous phosphorylation of neuronal nitric oxide synthase. The intrahippocampal infusion of 7-nitro-indazole, 2-[N-(2-hidroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, or 2-amino-5-phosphonopentanoic acid disrupted inhibitory avoidance learning. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that these drugs significantly depressed phosphorylation of hippocampal nitric oxide synthase. The Ca2+-independent activity of hippocampal calcium/calmodulin-dependent protein kinase II was significantly lower in the 2-[N-(2-hidroxyethyl)-N-(4-methoxy-benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine or the 2-amino-5-phosphonopentanoic acid-infused group compared with the controls. Although these depressed activities were not reversed by the infusion of a nitric oxide donor (sodium nitroprusside), this did significantly improve the rats' inhibitory avoidance deficit. These results, taken together, indicate that the nitric oxide synthase activation is essential for inhibitory avoidance learning, which may be triggered via the calcium/calmodulin-dependent protein kinase II activation in the hippocampus.

Animals↗
PubMed1985

Serial ablations of the telencephalon and avoidance learning by goldfish (Carassius auratus).

Simultaneous bilateral ablation of the teleost telencephalon was confirmed to dramatically impair the retention, extinction, and "reversal learning" of a preoperatively learned instrumental avoidance response in a shuttle box. The focus of the experiment was on whether two-stage serial unilateral ablations of the teleost telencephalon would ameliorate the effects seen following one-stage bilateral ablation and whether such amelioration would be a function of the fish's experiences between the staged ablations. The degree of retention, relearning, and extinction of the avoidance response was not modulated by the serial ablation procedure whether or not there was interoperation retraining experience. However, reversal learning, in which the previous warning signal became the safety signal and the previous safety signal became the new warning signal, was less impaired following serial ablations than following single-stage bilateral ablation. These results are contrasted with those from experiments with mammalian subjects.

Animals↗
PubMed1997

Amygdalar lesions block discriminative avoidance learning and cingulothalamic training-induced neuronal plasticity in rabbits.

Learning to fear dangerous situations requires the participation of neurons of the amygdala. Here it is shown that amygdalar neurons are also involved in learning to avoid dangerous situations. Amygdalar lesions severely impaired the acquisition of acoustically cued, discriminative instrumental avoidance behavior of rabbits. In addition, the development of anterior cingulate cortical and medial dorsal thalamic training-induced neuronal plasticity in the early stages of behavioral acquisition was blocked in rabbits with lesions. The development of training-induced neuronal plasticity in the medial dorsal and anterior thalamic nuclei in late stages of behavioral acquisition was also blocked in rabbits with lesions. These results indicate that the integrity of the amygdala is essential for the establishment of both early and late training-induced cingulothalamic neuronal plasticity. It is hypothesized that amygdalar training-induced neuronal plasticity in the initial trials of conditioning represents a substrate of learned fear, essential for the early and late cingulothalamic plasticity that is involved in mediation of acquisition of the instrumental avoidance response.

Amygdala↗
PubMed1999

Strain distribution of mice in discriminated Y-maze avoidance learning: genetic and procedural differences.

The current study was conducted to characterize discriminated avoidance learning in mice by using a Y-maze task. In Experiment 1, the task parameters were manipulated, including the amount of time spent in the start arm, the amount of time to make the avoidance response, and the intertrial interval (ITI) using C57 x SJL F1 hybrid mice. Avoidance performance was significantly improved with longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4 inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57 x SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain differences were observed in avoidance learning, with BALB, DBA, C57 x SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice. These data demonstrate that Y-maze performance is significantly influenced by the genetic background of the mouse and the parameters of the task.

Animals↗
PubMed2006

Long-term consequences of early experience on adult avoidance learning in female rats: role of the dopaminergic system.

Following our hypothesis that juvenile emotional and/or cognitive experience should affect learning performance at preweaning age as well as adulthood, the present study in female Wistar rats aimed to examine the impact of (i) avoidance training at preweaning age, (ii) exposure to repeated maternal separation, (iii) the combination of both, and (iv) the blockade of dopaminergic neurotransmission on adult two-way active avoidance learning in rats. We found that preweaning, i.e. three week old, rats were less capable of avoidance learning compared to adults. Our main findings revealed that preweaning avoidance training alone improved avoidance learning in adulthood. Furthermore, maternal separation alone also improved avoidance learning in preweaning and in adult rats, but this effect of maternal separation did not add up to the beneficial effect of preweaning avoidance training on adult learning. In addition, the pharmacological blockade of dopamine receptors during preweaning avoidance training via systemic application of haloperidol impaired preweaning avoidance performance in a dose-dependent manner. Testing the haloperidol-treated preweaning presumed "non-learners" as adults revealed that they still showed improved learning as adults. Taken together, our results strongly support the hypothesis that emotional as well as cognitive experience at preweaning age leaves an enduring "memory trace," which can facilitate learning in adulthood. Our pharmaco-behavioral studies suggest that unlike the adult brain, preweaning learning and memory formation is less dependent on dopaminergic mechanisms, which raises the intriguing question of possible alternative pathways.

Age Factors↗
PubMed1988

Infrapyramidal mossy fibers and two-way avoidance learning: developmental modification of hippocampal circuitry and adult behavior of rats and mice.

The extent of the intra- and infrapyramidal mossy fiber projection (IIP-MF) in the hippocampus of mice and rats is strain-specific, and correlates negatively with the strain-specific capacity of avoidance learning. If variations of the IIP-MF influence the capacity for 2-way avoidance learning, then developmental modification of the IIP-MF projection in an individual member of a strain should remain correlated with its adult behavior. Pups of strains with high avoidance capacity and small IIP-MF projections (RHA rats, DBA/2 and BALB/c mice) were injected with varying doses of thyroxine during the postnatal period. This transient hyperthyroidism resulted in a strong, yet largely unpredictable, variability of the IIP-MF projection in the adult animals. Furthermore, postnatal saline injections also increased the variability of the IIP-MF projection; however, this was to a lesser degree than when using thyroxine. The animals were tested for 2-way avoidance learning at the age of 90-120 d. Many showed strain-atypical avoidance scores. These deviations from the inherited level of 2-way avoidance learning were strongly correlated with the magnitude of the IIP-MF projection, regardless of whether the structural changes resulted from thyroxine or saline injections. A multivariate analysis showed that the observed correlations could neither be explained by thyroxine-induced changes in brain weight nor by individual differences of other terminal fields in the hippocampal region CA3. These results suggest that the extent of the IIP-MF projection is influenced by several genetic and epigenetic factors. Irrespective of the underlying causes, the magnitude of the IIP-MF (or of an unknown but well-correlated variable) appears to bias the adult capacity for 2-way avoidance learning predictably.

Animals↗
PubMed1985

Forebrain serotonergic involvement in avoidance learning.

The one-way active avoidance deficit caused by the serotonergic (5-HT) releasing compound p-chloroamphetamine (PCA) was examined in rats after degeneration of 5-HT neurons in the forebrain. Injection of 5,7-dihydroxytryptamine (5,7-DHT) into the forebrain in desipramine (20 mg/kg)-pretreated rats resulted in a 65-70% decrease in 5-HT concentrations in the prefrontal cortex and hippocampus without any significant effect on striatal 5-HT. Slight reductions in noradrenaline (NA) (25%) and dopamine (DA) (34%) concentrations were observed in the prefrontal cortex only. The 5,7-DHT lesions markedly attenuated the impaired avoidance performance induced by PCA (2.5 mg/kg), suggesting that the avoidance deficit depends on intact 5-HT terminals in cortex and/or hippocampus. The 5,7-DHT lesion alone caused a slight but significant impairment of acquisition. The results suggest that 5-HT terminal systems in the forebrain play an important role in avoidance learning.

5,7-Dihydroxytryptamine↗