Biomedical subjects

C Sandi

Publications and source records attributed to C Sandi.

At least 19 recordsLinked to original sources

PubMed2006

Selective learning and memory impairments in mice deficient for polysialylated NCAM in adulthood.

The neural cell adhesion molecule (NCAM) has been implicated in regulating synaptic plasticity mechanisms as well as memory consolidation processes. Attachment of polysialic acid to NCAM (PSA-NCAM) has been reported to down-regulate its adhesive forces, a process hypothesized to be implicated in synapse selection after learning experiences. PSA-NCAM has been critically implicated in hippocampus-related synaptic plasticity and memory storage, but information about its functional role in other brain areas remains scarce. Here, we studied mice deficient for polysialyltransferase-1 (ST8SialV/PST-1), an enzyme which attaches PSA to NCAM during postnatal development and adulthood, and whose deficiency results in a drastic reduction of PSA-NCAM expression throughout the brain in adulthood. Mice were tested for their performance in the water maze and auditory fear conditioning (AFC). We report that ST8SiaIV knockout mice were impaired in spatial as well as reversal learning in the water maze. On the other hand, AFC was intact and ST8SiaIV mice exhibited no impairments in the acquisition or retention of cued fear memories. Spatial orientation learning and reversal learning require complex integration of spatial information and response selection involving the hippocampus and prefrontal cortex, whereas cued fear conditioning is an associative type of emotional memory that highly depends on amygdala function. Therefore, our results indicate that PSA-NCAM contributes differentially to learning processes that differ in the nature of the neural computations involved, which probably reflects a differential role of this molecule in different brain regions.

Amygdala↗

PubMed2006

Chronic restraint stress induces changes in synapse morphology in stratum lacunosum-moleculare CA1 rat hippocampus: a stereological and three-dimensional ultrastructural study.

Chronic restraint stress is known to affect the morphology and synaptic organization of the hippocampus, predominantly within CA3 but also in CA1 and dentate gyrus. In this study, we provide the first evidence for specific ultrastructural alterations affecting asymmetric axo-spinous synapses in CA1 stratum lacunosum-moleculare following chronic restraint stress (6 h/day, 21 days) in the rat. The structure of asymmetric axo-spinous post-synaptic densities was investigated using serial section three-dimensional reconstruction procedures in control (n=4) and chronic restraint stress (n=3) animals. Dendritic spine profiles (spine head+neck) associated with the sampled synaptic contacts (30 per animal) were also reconstructed in three-dimensions. Morphometric analyses revealed a significant increase in post-synaptic density surface area (+36%; P=0.03) and a highly significant increase in post-synaptic density volume (+79%; P=0.003) in the chronic restraint stress group. These changes were directly associated with 'non-macular' (perforated, complex and segmented) post-synaptic densities. A highly significant overall increase in the 'post-synaptic density surface area/spine surface area' ratio was also detected in the chronic restraint stress group (+27%; P=0.002). In contrast, no quantitative changes in spine parameters were found between groups. The Cavalieri method was used to assess the effects of chronic restraint stress exposure upon CA1 hippocampal volume. The mean volume of total dorsal anterior CA1 hippocampus was significantly lower in the chronic restraint stress group (-16%; P=0.036). However, when corrected for volume changes, no significant alteration in a relative estimate of the mean number of asymmetric axo-spinous synapses was detected in CA1 stratum lacunosum-moleculare between control and chronic restraint stress groups. The data indicate a structural remodeling of excitatory axo-spinous synaptic connectivity in rat CA1 stratum lacunosum-moleculare as a result of chronic restraint stress.

Animals↗

PubMed2005

Differences in corticosterone level due to inter-food interval length: implications for schedule-induced polydipsia.

The purpose of this study was to determine the effects of different food-reinforcement schedules on plasma corticosterone (CORT), and its possible involvement in the acquisition and maintenance of schedule-induced polydipsia (SIP). In Experiment 1, three groups of rats were submitted to two different fixed-interval (FI) schedules with inter-food intervals of 30 and 120 s, and to a massed-feeding presentation for 40 days until SIP was well stabilized. In Experiment 2, six groups of rats were exposed to the same schedules, FI 30s and FI 120s, and to the massed-feeding condition, but no water bottles were presented. CORT levels were determined on Days 3 and 40. Results of Experiment 1 indicated that FI 30s schedule, but not FI 120s or the massed-feeding condition, induces excessive drinking from Day 3. Results in Experiment 2 indicated that CORT levels were similar for all the groups on Day 3. However, only animals on the FI 30s schedule did increase their CORT levels on Day 40, with no variation in the hormone in the other two conditions, FI 120s and massed-feeding presentations. The data are discussed in terms of the implications of these results for hypotheses of SIP as anxiolitic behavior.

Animals↗

PubMed2005

Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: a three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities.

Chronic stress and spatial training have been proposed to affect hippocampal structure and function in opposite ways. Previous morphological studies that addressed structural changes after chronic restraint stress and spatial training were based on two-dimensional morphometry which does not allow a complete morphometric characterisation of synaptic features. Here, for the first time in such studies, we examined these issues by using three-dimensional (3-D) reconstructions of electron microscope images taken from thorny excrescences of hippocampal CA3 pyramidal cells. Ultrastructural alterations in postsynaptic densities (PSDs) of thorny excrescences receiving input from mossy fibre boutons were also determined, as were changes in numbers of multivesicular bodies (endosome-like structures) within thorny excrescences and dendrites. Quantitative 3-D data demonstrated retraction of thorny excrescences after chronic restraint stress which was reversed after water maze training, whilst water maze training alone increased thorny excrescence volume and number of thorns per thorny excrescence. PSD surface area was unaffected by restraint stress but water maze training increased both number and area of PSDs per thorny excrescence. In restrained rats that were water maze trained PSD volume and surface area increased significantly. The proportion of perforated PSDs almost doubled after water maze training and restraint stress. Numbers of endosome-like structures in thorny excrescences decreased after restraint stress and increased after water maze training. These findings demonstrate that circuits involving contacts between mossy fibre terminals and CA3 pyramidal cells at stratum lucidum level are affected conversely by water maze training and chronic stress, confirming the remarkable plasticity of CA3 dendrites. They provide a clear illustration of the structural modifications that occur after life experiences noted for their different impact on hippocampal function.

Animals↗

PubMed2005

Chronic restraint stress down-regulates amygdaloid expression of polysialylated neural cell adhesion molecule.

The amygdala is a brain area which plays a decisive role in fear and anxiety. Since exposure to chronic stress can induce profound effects in emotion and cognition, plasticity in specific amygdaloid nuclei in response to prior stress has been hypothesized to account for stress-induced emotional alterations. In order to identify amygdala nuclei which may be affected under chronic stress conditions we evaluated the effects of 21-days chronic restraint stress on the expression of a molecule implicated crucially in alterations in structural plasticity: the polysialylated neural cell adhesion molecule. We found that polysialylated neural cell adhesion molecule-immunoreactivity within the amygdala, present in somata and neuronal processes, has a regional gradient with the central medial and medial amygdaloid nuclei showing the highest levels. Our results demonstrate that chronic restraint stress induced an overall reduction in polysialylated neural cell adhesion molecule-immunoreactivity in the amygdaloid complex, mainly due to a significant decrease in the central medial amygdaloid and medial amygdaloid nuclei. Our data suggest that polysialylated neural cell adhesion molecule in these nuclei may play a prominent role in functional and structural remodeling induced by stress, being a potential mechanism for cognitive and emotional modulation. Furthermore, these finding provide the first clear evidence that life experiences can regulate the expression of polysialylated neural cell adhesion molecule in the amygdaloid complex.

Amygdala↗

PubMed2004

Spatial learning impairment induced by chronic stress is related to individual differences in novelty reactivity: search for neurobiological correlates.

Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothesized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find a neurobiological substrate that specifically correlated with the differential cognitive vulnerability to chronic stress shown by animals with a different novelty reactivity, this study confirms the hypothesis that rats differ in their susceptibility to display stress-induced impairments in hippocampus-dependent spatial learning tasks. In addition, it provides a model to further search for the neurobiological substrate(s) involved in the differential susceptibility to develop stress-induced cognitive impairments.

Analysis of Variance↗

PubMed2003

Post-training administration of a synthetic peptide ligand of the neural cell adhesion molecule, C3d, attenuates long-term expression of contextual fear conditioning.

The neural cell adhesion molecule (NCAM) plays a key role in synaptic plasticity and memory formation. We have recently developed a synthetic peptide, termed C3d, which, through the binding to the first, N-terminal immunoglobulin-like (Ig) module in the extracellular portion of NCAM, has been shown to promote neurite outgrowth and synapse formation in vitro, and to interfere with passive avoidance memory in rats in vivo. In this study, we investigated whether the i.c.v. administration of C3d, either 5.5 h after or 2 days before training, could be effective to modulate the strength at which emotional memory for aversive situations is established into a long-term memory. The effects of the peptide were evaluated in adult male Wistar rats trained in the contextual fear conditioning task. The results indicated that C3d significantly reduced the subsequent long-term retention of the conditioned fear response when administered 5.5 h post-training, as indicated by retention tests performed 2-3 and 7 days post-training. However, this treatment failed to influence conditioning for this task when injected 2 days pre-training. Additional experiments showed that C3d did not influence the emotional or locomotor behaviour of the animals, when tested in the open field task. Furthermore, hippocampal levels of microtubule-associated protein 2 (MAP2), Synaptophysin and NCAM were found unchanged when evaluated by enzyme-linked immunosorbent assay in crude synaptosomal preparations 2 days after peptide i.c.v. injection. Therefore, post-training injection of this synthetic peptide was efficient to attenuate the strength at which memory for contextual fear conditioning was enduringly stored, whilst it did not affect the acquisition of new memories. In addition to further support the view that NCAM is critically involved in memory consolidation, the current findings suggest that the NCAM IgI module is a potential target for the development of therapeutic drugs capable to reduce the cognitive impact induced by exposure to intensive stress experiences.

Animals↗

PubMed2003

Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits.

Brain development and function are dependent on thyroid hormone (T3), which acts through nuclear hormone receptors. T3 receptors (TRs) are transcription factors that activate or suppress target gene expression in a hormone-dependent or -independent fashion. Two distinct genes, TRalpha and TRbeta, encode several receptor isoforms with specific functions defined in many tissues but not in the brain. Mutations in the TRbeta gene cause the syndrome of peripheral resistance to thyroid hormone; however, no alterations of the TRalpha gene have been described in humans. Here we demonstrate that mice lacking the TRalpha1 isoform display behavioral abnormalities of hippocampal origin, as shown by the open field and fear conditioning tests. In the open field test mutant mice revealed less exploratory behavior than wild-type mice. In the contextual fear conditioning test mutant mice showed a significantly higher freezing response than wild-type controls when tested 1 week after training. These findings correlated with fewer GABAergic terminals on the CA1 pyramidal neurons in the mutant mice. Our results indicate that TRalpha1 is involved in the regulation of hippocampal structure and function, and raise the possibility that deletions or mutations of this receptor isoform may lead to behavioral changes or even psychiatric syndromes in humans.

Animals↗

PubMed2002

Chronic stress induces opposite changes in the mRNA expression of the cell adhesion molecules NCAM and L1.

The effects of 21-day exposure to restraint stress on mRNA levels of the cell adhesion molecules NCAM and L1 were evaluated in different hippocampal regions (CA1, CA3, and dentate gyrus) and other structures (thalamus, prefrontal and frontal cortices, and striatum) of the rat brain. A general decrease in gene expression of the neural cell adhesion molecule (NCAM) was found throughout the brain, particularly in all hippocampal subregions. On the contrary, transcripts for the adhesion molecule L1 were specifically increased at the level of the hippocampus, especially in the dorsal dentate gyrus and area CA3. mRNA for the NCAM180 isoform was detected unchanged in all brain areas examined after chronic stress. A second experiment explored whether there would be cognitive alterations associated with this stress procedure and molecular regulation. Thus, after exposure to the same restraint regimen, performance in the water maze was evaluated. Although stressed rats displayed the ability to learn the task throughout the training session, they showed a transient deficit in the initial phase of the acquisition. In conclusion, our findings indicate that chronic stress interferes with the mechanisms involved in the synthesis of cell adhesion molecules of the immunoglobulin superfamily. Furthermore, they suggest that these effects might be involved in the mechanisms by which stress induces structural and functional alterations in the central nervous system and, particularly, in the hippocampus.

Animals↗

PubMed2002

Chronic restraint stress induces an isoform-specific regulation on the neural cell adhesion molecule in the hippocampus.

Existing evidence indicates that 21-days exposure of rats to restraint stress induces dendritic atrophy in pyramidal cells of the hippocampus. This phenomenon has been related to altered performance in hippocampal-dependent learning tasks. Prior studies have shown that hippocampal expression of cell adhesion molecules is modified by such stress treatment, with the neural cell adhesion molecule (NCAM) decreasing and L1 increasing, their expression, at both the mRNA and protein levels. Given that NCAM comprises several isoforms, we investigated here whether chronic stress might differentially affect the expression of the three major isoforms (NCAM-120, NCAM-140, NCAM-180) in the hippocampus. In addition, as glucocorticoids have been implicated in the deleterious effects induced by chronic stress, we also evaluated plasma corticosterone levels and the hippocampal expression of the corticosteroid mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). The results showed that the protein concentration of the NCAM-140 isoform decreased in the hippocampus of stressed rats. This effect was isoform-specific, because NCAM-120 and NCAM-180 levels were not significantly modified. In addition, whereas basal levels of plasma corticosterone tended to be increased, MR and GR concentrations were not significantly altered. Although possible changes in NCAM-120, NCAM-180 and corticosteroid receptors at earlier time points of the stress period cannot be ignored, this study suggests that a down-regulation of NCAM-140 might be implicated in the structural alterations consistently shown to be induced in the hippocampus by chronic stress exposure. As NCAM-140 is involved in cell-cell adhesion and neurite outgrowth, these findings suggest that this molecule might be one of the molecular mechanisms involved in the complex interactions among neurodegeneration-related events.

Animals↗

PubMed2001

Effects of chronic stress on contextual fear conditioning and the hippocampal expression of the neural cell adhesion molecule, its polysialylation, and L1.

Chronic stress has been shown to induce time-dependent neurodegeneration in the hippocampus, ranging from a reversible damage to a permanent neuronal loss. This damage has been proposed to impair cognitive function in hippocampus-dependent learning tasks. In this study, we have used a 21-day restraint stress procedure in rats, previously reported to induce reversible atrophy of apical dendrites of CA3 pyramidal cells, to assess whether it may influence subsequent performance in the contextual fear conditioning task under experimental conditions involving high stress levels (1 mA shock intensity as the unconditioned stimulus). In addition, we were interested in the study of the possible cellular and molecular mechanisms involved in the reversible phase of neural damage. Cell adhesion molecules of the immunoglobulin superfamily, such as the neural cell adhesion molecule and L1, are cell-surface macromolecules that, through their recognition and adhesion properties, regulate cell-cell interactions and have been reported to play a key role in cognitive functioning. A second aim of this study was to evaluate whether chronic stress would modulate the expression of the neural cell adhesion molecule, its polysialylation, and L1 in the hippocampus. The results showed that chronic stress facilitated subsequent contextual fear conditioning. They also showed that chronically stressed rats displayed reduced hippocampal neural cell adhesion molecule, but increased polysialylated expression as well as a trend towards exhibiting increased L1 expression. In summary, these results support the view that a 21-day chronic stress regimen predisposes individuals to develop enhanced contextual fear conditioning responses. They also indicate that cell adhesion molecules might play a role in the structural remodelling that occurs in the hippocampus as a consequence of chronic stress exposure.

Animals↗

PubMed2001

Differential activation of hippocampus and amygdala following spatial learning under stress.

We examined the activation of memory-related processes in the hippocampus and the amygdala following spatial learning under stress, in the rat. Animals were trained in a water maze in a massed spatial task under two stress conditions (cold and warm water). In the dorsal CA1, training was accompanied by increased phosphorylation of ERK2 only in animals that have acquired the task (irrespective of whether they were trained in cold or warm water). In the amygdala, significant activation of ERK2 was found only in animals that learned the task well under high levels of stress. Hence, the results suggest that the amygdala and the hippocampus are differentially activated following spatial learning, depending on the level of stress involved.

Amygdala↗

PubMed2001

Stress alleviates reduced expression of cell adhesion molecules (NCAM, L1), and deficits in learning and corticosterone regulation of apolipoprotein E knockout mice.

Cell adhesion molecules (CAMs) involved in synaptic changes underlying learning and memory processes, are implicated in the effect of stress on behavioural performance. The present study was designed to test the hypothesis that (i) expression of CAMs is apolipoprotein E- (apoE) genotype dependent and (ii) repeated exposure to stress modulates the synthesis of CAMs in an apoE-genotype dependent manner. Using ELISA we tested this hypothesis and measured expression of NCAM and L1 in different brain regions of naïve and stressed apolipoprotein E-knockout (apoE0/0) and C57Bl6 (wild-type) mice. Naïve apoE0/0 mice had elevated basal morning corticosterone and ACTH concentrations and decreased expression of NCAM and L1 compared to wild-type mice. Repeated exposure of mice to rats, as the common stressor, alleviated the reduction in expression of CAMs in apoE0/0 mice; seven days after the last rat exposure, expression of NCAM was increased in frontal brain and hippocampus whereas expression of L1 was increased in hippocampus and cerebellum. Rat stress attenuated the elevation of basal morning corticosterone concentration in apoE0/0 mice towards concentrations detected in wild-type mice. Moreover, rat stress improved learning and memory of apoE0/0 mice in the water maze. In conclusion, repeated exposure to stress eliminated apoE-genotype-related differences in expression of CAMs. Under these same conditions the differences in cognitive performance and corticosterone concentrations were abolished between wild type and apoE0/0 mice.

Adrenocorticotropic Hormone↗

PubMed2000

Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity.

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily, NCAM and L1, as well as the post-translational addition of alpha-2, 8-linked polysialic acid (PSA) homopolymers to NCAM (PSA-NCAM), have been implicated in the neural mechanisms underlying memory formation. Given that the degree of stress elicited by the training situation is one of the key factors that influence consolidation processes, this study questioned whether training rats under different stressor intensities (0.2, 0.4, or 1 mA shock intensity) in a contextual fear conditioning task might regulate subsequent expression of NCAM, PSA-NCAM and L1 in the hippocampus, as evaluated immediately after testing rats for conditioning at 12 and 24 h after training. Behavioural inhibition (evaluated as a 'freezing' index) at testing and post-testing plasma corticosterone levels were also assessed. The results showed that 12 h post-training, conditioned animals displayed reduced NCAM, but increased L1, expression. At this time point, the group trained at the highest shock intensity (1 mA) also presented decreased PSA-NCAM expression. Analyses performed 24 h post-training indicated that the 1 mA group exhibited increased NCAM and L1 expression, but decreased expression of PSA-NCAM levels. In addition, L1 values that presented a shock intensity-dependent U-shaped pattern were also increased in the group trained at the lowest shock condition (0.2 mA) and remained unchanged in the intermediate shock condition (0.4 mA). Freezing and corticosterone values at both testing times were positively related with shock intensity experienced at training. Therefore, our results show a complex regulation of CAMs of the immunoglobulin superfamily in the hippocampus that depends upon stressor intensity and time factors. In addition, the pattern of CAMs expression found in the 1 mA group (which is the one that shows higher post-training corticosterone levels and develops the stronger and longer-lasting levels of fear conditioning) supports the view that, after a first phase of synaptic de-adherence during consolidation, NCAM and L1 might participate in the stabilization of selected synapses underlying the establishment of long-term memory for contextual fear conditioning, and suggests that glucocorticoids might play a role in the observed regulation of CAMs.

Animals↗

PubMed1999

Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments.

The temporal pattern of exposure to glucocorticoids has been reported to be a critical factor in determining the outcome of glucocorticoid actions at the brain. In this work, the effects of different regimes of subcutaneous corticosterone administration (acute-single injection-vs. chronic-daily injection for 21 days) on the expression of the neural cell adhesion molecule (NCAM) were evaluated in different rat brain regions (CA1-CA4, dentate gyrus, frontal cortex, striatum, and hypothalamus). The treatments were selected according to previous studies in which we showed biphasic effects of corticosterone on memory formation, with acute corticosterone effects being facilitating and chronic effects being deleterious. In addition, the chronic treatment was shown by others to result in structural alterations at the hippocampus. NCAM was evaluated given its cell-cell recognition and adhesion properties, and the involvement on synaptic stabilisation subserving long-term memory formation. The results showed a biphasic modulation of NCAM levels at the frontal cortex, with acute corticosterone resulting in enhanced NCAM levels at 8 h and 24 h posttraining, and the chronic treatment decreasing its expression. None of the other brain areas examined showed significant changes in NCAM expression with corticosterone treatments, except for the hypothalamus that showed reduced NCAM levels after the chronic corticosterone regime. These results support the view that NCAM regulation at the frontal cortex might be a mechanism by which corticosterone treatments influence memory formation. They also highlight the hypothalamus as a brain area particularly sensitive to NCAM regulation by prolonged exposure to elevated glucocorticoids.

Animals↗

PubMed1998

A role for brain glucocorticoid receptors in contextual fear conditioning: dependence upon training intensity.

We studied the possible involvement of corticosteroids in the establishment and long-term expression of contextual fear conditioning and questioned whether a corticosteroid action might be dependent upon stimulus intensity at training. Experiments included: (i) the intracerebroventricular administration of specific antagonists for the two types of intracellular corticosteroid receptors to rats trained at either 1 mA or 0.4 mA shock intensity at conditioning; and (ii) the administration of corticosterone after conditioning rats to 0.2 mA shocks. The results showed that the administration of a type II glucocorticoid, but not a type I mineralocorticoid, receptor antagonist before conditioning rats to the intermediate shock condition attenuated long-term expression of contextual fear conditioning. However, treatment with the antagonists before conditioning to the high shock intensity failed to influence the extent of fear conditioning. In addition, an intraperitoneal corticosterone injection, given immediately after training rats at the low shock intensity, enhanced long-term expression of the fear response. The results support the view that post-training levels of circulating corticosterone, through an interaction with central type II glucocorticoid receptors, modulate the strength to which memory for contextual fear conditioning is established and maintained.

Animals↗

PubMed1998

Correlational relationship between shock intensity and corticosterone secretion on the establishment and subsequent expression of contextual fear conditioning.

A role for corticosterone in the consolidation of contextual fear conditioning has previously been proposed. In this study, physiological evidence was found to support this view. The extent of conditioned fear and the levels of plasma corticosterone in rats, after context exposure at training and at different posttraining times (24 hr and 7 days), depended on the intensity of the unconditional stimulus (footshock). In each experimental session, a positive correlation was found between the magnitude of corticosterone levels and the fear-related behavioral inhibition exhibited in the context. Results support the involvement of corticosterone on the processes that occur during consolidation in determining the strength at which the contextual fear conditioning is stored as a long-term memory.

Analysis of Variance↗

PubMed1998

Piracetam facilitates long-term memory for a passive avoidance task in chicks through a mechanism that requires a brain corticosteroid action.

We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version of this task--whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10 h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.) increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in this learning model, requires the activation of the two types of intracellular corticosteroid receptors.

Adrenal Cortex Hormones↗