Biomedical subjects

R A Prado-Alcalá

Publications and source records attributed to R A Prado-Alcalá.

At least 19 recordsLinked to original sources

PubMed2006

Follow-up study of learning-disabled children treated with neurofeedback or placebo.

This report is a 2-year follow-up to a previous study describing positive behavioral changes and a spurt of EEG maturation with theta/alpha neurofeedback (NFB) training in a group of Learning Disabled (LD) children. In a control paired group, treated with placebo, behavioral changes were not observed and the smaller maturational EEG changes observed were easily explained by increased age. Two years later, the EEG maturational lag in Control Group children increased, reaching abnormally high theta Relative Power values; the absence of positive behavioral changes continued and the neurological diagnosis remained LD. In contrast, after 2 years EEG maturation did continue in children who belonged to the Experimental Group with previous neurofeedback training; this was accompanied by positive behavioral changes, which were reflected in remission of LD symptoms.

Biofeedback, Psychology↗

PubMed2001

Dose- and time-dependent scopolamine-induced recovery of an inhibitory avoidance response after its extinction in rats.

The present investigation was aimed at elucidating the dose and time dependency of scopolamine-induced recovery of inhibitory avoidance after its extinction. Two experiments were conducted: in the first, we analyzed the effects of four doses (1, 2, 4, and 8 mg/kg) of the musacrinic receptor antagonist scopolamine, on the expression of this conditioned response once it had been extinguished. Independent groups of rats were trained in a one-trial, step-through inhibitory avoidance task and submitted to daily retention (extinction) tests. After extinction had occurred, animals were injected intraperitoneally 10 min before retention testing, either with saline or scopolamine. Results show that scopolamine produced a dose-dependent recovery of the avoidance response. The second experiment was carried out in the same animals, which were now tested for retention of inhibitory avoidance at 1, 2, 3, 6, and 9 months after completion of the first experiment. All rats received counterbalanced injections of saline or scopolamine 10 min before testing at each time interval. Reliable recovery of the avoidance response was observed at the 1-month interval with a clear dose dependency while, after the second month, only the groups treated with the two higher doses continued responding. The results indicate that recovery of the extinguished response produced by muscarinic blockade follows dose- and time-dependent curves, and can be achieved long after a single training session. These data suggest that the inhibitory avoidance memory trace is retained in the brain after behavioural extinction of this response, thus supporting the view of extinction as new learning that affects the retrieval of the original memory, but does not modify its storage.

Animals↗

PubMed2000

Cortistatin modulates memory processes in rats.

Cortistatin (CST) is a recently described neuropeptide with high structural homology with somatostatin. Its mRNA is restricted to gamma amino butyric acid (GABA)-containing cells in the cerebral cortex and hippocampus. CST modulates the electrophysiology of the hippocampus and cerebral cortex of rats; hence, it may be modulating mnemonic processes. In this study, we have evaluated the effect of CST and somatostatin (SS) on short- and long-term memory (STM and LTM, respectively), as well as on the extinction of the behavior by using the footshock passive avoidance behavioral test. In addition, we tested the ability of both neuropeptides to affect the generation of cAMP in hippocampal neurons in culture. Results showed that the administration of either CST or SS into the hippocampal CA1 deteriorates memory consolidation in a dose-response fashion and facilitates the extinction of the learned behavior. CST was more potent than SS. Likewise, CST increases cAMP while SS decreases it. These results strongly support a modulatory role for CST in memory processes.

Animals↗

PubMed1998

Differential effects of unilateral lidocaine infusion into the globus pallidus on consolidation and performance of inhibitory avoidance.

The striatum is involved in memory consolidation; also involved in this process is one of its two major efferent targets, namely, the substantia nigra. It is not clear, however, if the other target, the globus pallidus, participates in storage and/or performance of learned information. To examine this problem, male Wistar rats were trained in an inhibitory avoidance task and tested for retention 24 h afterward. Independent groups were infused, unilaterally, with 2% lidocaine in the pallidus either 2 min after training or 2 min before testing. No disturbances of memory were detected with posttraining infusion, but a significant deficit in retention was observed as a consequence of pretest infusion. Infusion of isotonic saline into the globus pallidus, or of lidocaine before testing into the parietal cortex, after training into the ventral thalamic nucleus, and both before training and testing into this thalamic nucleus were without effect. Taken together, the data indicate that unilateral inactivation of the GP interferes with retrieval of information derived from inhibitory avoidance training, but not with the early stages of memory consolidation of this task, and other work indicates that the pallidus may be involved in a late phase of this process.

Anesthetics, Local↗

PubMed1998

Striatal transplants prevent AF64A-induced retention deficits.

The relevance of the cholinergic system in mnemonic processes has been repeatedly demonstrated. In addition to the cholinergic systems that project to the telencephalon, there are subcortical nuclei with intrinsic cholinergic cells which appear to be involved in memory consolidation; among these is the striatum. Intrastriatal administration of anticholinergic drugs, as well as excitotoxic and electrolytic lesions have been shown to disrupt the acquisition and retention of instrumentally conditioned behaviors. In the present study male Wistar rats were used to confirm the reported detrimental effects of striatal lesions produced by the cholinotoxin AF64A on long-term retention (LTR) of inhibitory avoidance and spontaneous locomotor activity, to determine its effects on short-term retention (STR) and to investigate whether intrastriatal homotopic transplants can reverse the AF64A-induced behavioral deficits. AF64A-striatal lesions did not interfere with STR but disrupted LTR of the inhibitory avoidance task, and striatal transplants prevented this deficit. Spontaneous locomotor activity increased after the lesion but promptly returned to baseline levels. These results support previous findings showing striatal involvement in long-term but not short-term retention and indicate that homotopic transplants induce behavioral recovery of a learning task in striatal lesioned rats.

Acetylcholinesterase↗

PubMed1997

Selective M1 muscarinic receptor antagonists disrupt memory consolidation of inhibitory avoidance in rats.

The effect of three different M1 muscarinic antagonists, pirenzepine, biperiden, and trihexyphenidyl on memory consolidation was investigated. Rats were trained in a one-trial step-through inhibitory avoidance task and injected intraperitoneally immediately afterwards, either with pirenzepine, biperiden, or trihexyphenidyl (dose range from 0 to 16 mg/kg). The non-selective antimuscarinic compound scopolamine, was also administered for comparison. One day later, rats were tested for retention. Results show that biperiden, trihexyphenidyl and scopolamine produced a dose-dependent impairment of inhibitory avoidance consolidation, while pirenzepine had no effect. The amnestic state produced by biperiden and trihexyphenidyl was comparable to that observed after the administration of scopolamine. These results indicate that the selective blockade of the central M1 muscarinic receptors interfere with memory consolidation of inhibitory avoidance and suggest that this receptor subtype is critically involved in mnemonic functions.

Animals↗

PubMed1996

High level of footshock during inhibitory avoidance training prevents amnesia induced by intranigral injection of GABA antagonists.

Disruption of synaptic activity of a number of cerebral structures (e.g., neostriatum, amygdala, and thalamus) produces marked deficits in retention of instrumentally conditioned behaviors. When animals are given a relatively high number of training trials or high intensities of footshock during learning, however, such disruption is considerably less effective. Since there is a close anatomical and functional relationship between the neostriatum and the substantia nigra, it was of interest to determine whether enhanced training with a high level of footshock would prevent the reported amnesic state induced by injections of GABA antagonists into the latter structure. Rats were trained in a one-trial inhibitory task, using 0.2 or 0.4 mA, and then injected with microgram quantities of picrotoxin or bicuculline into the substantia nigra and posterior region of the zona incerta; retention was measured 24 h later. Only those groups that had been injected into the nigra and trained with 0.2 mA showed amnesia. These results support the hypotheses that (a) the normal activity of a set of structures is essential for the development of memory consolidation and (b) after an enhanced learning experience these structures may participate in memory consolidation, but are not necessary for the occurrence of this process.

Amnesia↗

PubMed1996

Effects of regional GABAergic blockade of the striatum on memory consolidation.

The prediction was made that blocking the action of gamma-aminobutyric acid (GABA) in different regions of the striatum, through local injection of picrotoxin, would produce differential amnestic effects. Rats were trained in an inhibitory avoidance task, and a retention test was carried out 24 h later. Posttraining injection of picrotoxin (1 microgram/1 microliter) into posteroventral and lateral regions produced strong amnesia; an intermediate degree of impairment was found when delivered at dorsomedial regions; and no retention deficit was found when given to the ventromedial aspect of the anterior striatum. In sum, the retention impairments were consistently higher in posterior and lateral striatal regions than in the anterior and medial regions. The present findings support the concept that striatal GABAergic activity is involved in memory functions and also provide further evidence of neurochemical heterogeneity within the striatum regarding memory consolidation.

Animals↗

PubMed1996

Changes in rat brain muscarinic receptors after inhibitory avoidance learning.

It is widely accepted that cerebral acetylcholine is necessary for learning and memory, but little is known about the type of muscarinic receptors involved in these functions. To investigate this problem, [3H]-N-methyl-scopolamine which binds to different types of muscarinic receptors, [3H]-Pirenzepine an M1 receptor antagonist, and [3H]-Oxotremorine-M which binds mainly to M2 receptors, were used as ligands to look for possible changes in muscarinic receptor density in neostriatum (NEO), hippocampus (HIP), amygdala (AMY), and temporo-parietal neocortex (CTX), after testing for retention of inhibitory avoidance, trained with high or low footshock intensities. After low reinforcement there was an M1 postsynaptic receptor up-regulation in NEO, HIP, and CTX, and an M2 presynaptic receptor down-regulation in HIP, which suggests a concerted pre- and postsynaptic cholinergic activation in this area. An up-regulation of both M1 and M2 receptors was detected in CTX of low and high footshocked animals, which indicates the presence of a cortical postsynaptic M2 receptor.

Amygdala↗

PubMed1995

Post-training injection of GABAergic antagonists into the striatum produces retrograde amnesia.

Although it is well established that the striatum contains both local and projection GABA neurons, little is known about their possible role in memory storage. We now report that in the Wistar rat, intrastriatal post-training injection of microgram quantities of bicuculine or picrotoxin, two GABA antagonists with different modes of action, induced retrograde amnesia of inhibitory avoidance, in concordance with the effects of injections of picrotoxin into the substantia nigra. These results suggest that GABA activity of the nigrostriatal system is involved in cognitive functions.

Amnesia, Retrograde↗

PubMed1994

Reversal of extinction by scopolamine.

The aim of this experiment was to determine the effects of muscarinic blockade on extinction of passive avoidance conditioning. Rats were trained with a foot shock of 2.5, 3.0, or 6.0 mA and were tested for retention for 8 weeks (once weekly). Five minutes before the seventh test they were injected with 8 mg/kg scopolamine. The groups that had been trained with 2.5 and 3.0 mA showed extinction, which was reversed by the scopolamine; the overreinforced group (6.0 mA) did not show extinction and the scopolamine did not alter the conditioned response. The data support the hypothesis that extinction represents the learning of a new response sustained by a set of cholinergic neurons, different from that which mediated original passive avoidance learning.

Acetylcholine↗

PubMed1994

Effects of central muscarinic blockade on passive avoidance: anterograde amnesia, state dependency, or both?

It was recently reported that administration of relatively high intensities of footshock (overreinforcement) during training of passive avoidance protected animals against the amnesic effect of scopolamine, injected 5 min after training. This was interpreted in terms of a lesser involvement of acetylcholine in memory consolidation. An alternative explanation was that overreinforcement accelerated the consolidation process, which could have taken place before the injection of scopolamine. To test for this possibility, male Wistar rats were injected with 4, 8, or 12 mg/kg of scopolamine, 5 min before training with low or high levels of footshock and then tested for retention of the task. Scopolamine induced the expected memory deficit after the low-intensity footshock; after overreinforcement the higher doses of scopolamine induced state dependency, while no deficits were produced with the lower dose. It was concluded that: (a) acetylcholine is indeed involved in memory consolidation of passive avoidance; (b) scopolamine interacts with high footshock levels to produce state dependency; and (c) when relatively low doses of scopolamine are used in conditions of overreinforcement, protection against scopolamine-induced amnesia becomes evident.

Amnesia↗

PubMed1993

Effects of GABA antagonists on inhibitory avoidance.

Experimental data indicate that GABA is involved in memory processes. However there are marked inconsistencies in the reported effects of interference with GABA synaptic activity on memory consolidation of aversively-motivated tasks. Both amnesia and improvement of performance have been reported after treatment with GABA antagonists. These contradictory effects could be explained by procedural differences in training. To test for this possibility rats were trained in passive avoidance using two levels of footshock and injected with a wide range of doses of picrotoxin and bicuculline. Picrotoxin did not modify the conditioned response while bicuculline induced amnesia only with the lower doses at both low and high footshock intensities. It was concluded that GABA is involved in memory consolidation, and that the conflicting results in the literature are indeed due, in part, to procedural differences, and also to the mode of action of these drugs.

Animals↗

PubMed1993

Intrastriatal injection of choline accelerates the acquisition of positively rewarded behaviors.

The prediction was made that by increasing the synthesis of striatal acetylcholine, through local injection of its precursor choline, the acquisition of a lever-pressing response in two different autoshaping situations would be accelerated. In the first experiment, choline was injected into the striatum or parietal cortex of rats immediately after dipper training; 24 h later and during 5 consecutive days the animals were submitted to an autoshaping procedure of the operant kind. In the second experiment, choline was administered to the same regions shortly after each of three classical-operant autoshaping sessions; during the next two sessions, autoshaping contingencies of the operant kind were in effect. In both experiments choline injection into the striatum induced a marked facilitation of acquisition of the conditioned responses, although cortical injection of choline produced a milder improvement only in the first experiment. These results indicate that striatal cholinergic activity is, indeed, involved in the early phases of positively reinforced learning.

Animals↗

PubMed1993

Protective effect of under-reinforcement of passive avoidance against scopolamine-induced amnesia.

Administration of antimuscarinic drugs induces amnesia of aversively motivated behaviors. However, when relatively high intensities of footshock are used during training (over-reinforcement), animals become protected against such amnesic state. Moreover, the protective effect is established in a none-or-all fashion, i.e., within a series of increasing intensities a minute augmentation of footshock intensity is sufficient to reach the protective threshold. In the present experiment it was found that very low intensities of aversive stimulation (under-reinforcement), sufficient to produce learning, also protected animals from scopolamine-induced amnesia. These results suggest that acetylcholine is critically involved in memory consolidation of passive avoidance, but only within a limited range of training intensities.

Amnesia↗

PubMed1991

Time-dependent effects of cholinergic blockade of the striatum on memory.

Rats were trained on a passive avoidance task, and a retention test was carried out 24 h later. Scopolamine was injected into the anterior striatum at one of various intervals following training: at 2 min it produced amnesia; an intermediate degree of impairment was found when given 8 min after training. With a delay of 15 min, this drug did not produce an interference with memory. These observations suggest that striatal cholinergic activity is involved in memory consolidation.

Amnesia↗

PubMed1990

Retrograde amnesia produced by intrastriatal atropine and its reversal by choline.

A number of studies have shown that cholinergic blockade of the striatum produces amnesia. In the present experiment it was predicted that by increasing the synthesis of striatal acetylcholine such amnesic state would be prevented. Atropine was injected into the striatum of rats before training of passive avoidance; some of these rats were also injected, intrastriatally, with choline before testing the retention of the task. Atropine alone produced amnesia while the combination of treatments reversed this effect.

Acetylcholine↗

PubMed1990

Is acetylcholine involved in memory consolidation of over-reinforced learning?

Systemic administration of anticholinergic drugs produces amnesia. To determine whether this effect can be prevented by increasing the magnitude of the learning experience, independent groups of rats were trained in passive avoidance, using a 3.0-mA footshock, and then injected with scopolamine (2, 4, 6, 8 or 12 mg/kg). When retention of the task was evaluated, a dose-dependent amnesic effect was found. When footshock intensity was increased to 6.0 and 9.0 mA, injections of 8 and 12 mg/kg of scopolamine did not produce memory impairments. These findings indicate that acetylcholine plays an important role in consolidation of passive avoidance, but it does not seem to be involved in memory processes when the magnitude of the negative reinforcer is increased.

Acetylcholine↗